| 00:00 | Mhm. Alright. So last lecture stopped on this slide if I recall |
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| 00:08 | . And we were talking about the much lina we're talking specifically a bunch |
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| 00:12 | loud and toxin Botox. And he you can draw things from nature. |
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| 00:18 | things can be toxic and poisonous can you sick. You can have it |
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| 00:22 | a controlled fashion. In the case Botox it will control them to control |
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| 00:28 | , vesicular acetylcholine fusion of the plasma and acetylcholine release therefore preventing muscle contractions |
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| 00:38 | the site where it was injected nearby can also be used for therapeutic reasons |
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| 00:47 | . Give Me 1 2nd Please. you can treat neurological disorders too as |
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| 00:54 | alluded. Mhm. So you can acetylcholine release along different pathways of the |
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| 01:03 | . You can control the secular You can control the presence of a |
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| 01:08 | Colin in the synapse. If you controlling a cyclical in restoration, you'll |
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| 01:12 | about that later in the lecture. can control it or you can control |
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| 01:17 | recycling of that neurotransmitter. And all these things are found in nature, |
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| 01:24 | usually by having some sort of a some sort of a disease. But |
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| 01:29 | usually applied and used for therapeutic purposes well. So you'll also learn more |
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| 01:35 | the function of the organophosphates. Then talked about three types of potentials and |
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| 01:42 | I review the E. P. . P. That we talked about |
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| 01:46 | and I PSB I'll remind you that started talking about the neuromuscular junction that |
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| 01:53 | pointed out several important things in the junction, skeletal muscle. There's only |
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| 02:00 | a single colony in post synaptic Nicotine exit polling reception means the synapses |
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| 02:07 | excited her. There's only one neurotransmitter released from motor neuron onto the muscles |
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| 02:13 | steel cone. When the synapses activated the civil coding is released, there's |
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| 02:20 | these molecules that get released of these of the synoptic clough. The structure |
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| 02:25 | the functional falls is such that the Akopian receptors are located most approximately to |
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| 02:33 | release size of the citadel colon. receptors, eligon gator or chemical gated |
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| 02:41 | channels and binding of a single Colin settle Colin receptors will open these receptor |
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| 02:50 | and will allow for influx of And you learn that these channels are |
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| 02:55 | to both sodium and potassium so they're specific to one ion but influx of |
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| 03:00 | will account for this massive deep polarization we call the And play potential or |
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| 03:07 | . P. P. In abbreviated . And to a potential is typically |
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| 03:12 | the order of 70 million votes. what makes us synapse high fidelity of |
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| 03:17 | to 1 but reliable when there is deep polarization and action potential prison |
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| 03:22 | That means that there's going to be a large enough deep polarization to reach |
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| 03:27 | threshold for actual potential and that deep from and playing potential. Once you |
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| 03:33 | this deep polarization that will engage other will engage both educated sodium channels, |
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| 03:40 | channels and producing muscle action potential muscles , they're also producing action country the |
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| 03:48 | and skeletal muscle action potentials are much in direction. So we discussed. |
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| 03:55 | you can when you think about the . P. S. Peace and |
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| 04:00 | mm plea for tom Charles, you think about here again that eh PSP's |
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| 04:10 | mps piece that will come back to the cns. They're typically half a |
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| 04:16 | volt once the now excited person So you have to engage many excited |
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| 04:22 | analysis in order to reach the threshold of the control generation. But and |
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| 04:28 | play potential. The TPP shown Red for the and play potential will |
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| 04:35 | massive enough to always reach that and that threshold and activate subsequently much longer |
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| 04:43 | insists than both educated sodium and both calcium channels. So in contrast excited |
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| 05:05 | boston optic potentials created in the N. S. By also wagon |
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| 05:13 | channels but in contrast are much smaller altitude. So a single synapse activation |
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| 05:20 | at 0.5 million balls. So if have many excitatory synapse sisters potential, |
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| 05:26 | not the potential is graded and it be half a mil of all if |
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| 05:31 | actually three synapses, 1.5 20 synopsis levels, 40 synopsis about 20 million |
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| 05:40 | . They're all excited. Tory they have to remember that these neurons will |
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| 05:44 | receiving inhibitory inputs to. That's not case in the neuromuscular junction. That's |
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| 05:49 | it's a very simple uh synaptic communication the level of more muscular junction for |
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| 05:58 | . P. S. P. excited to glutamate is going to get |
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| 06:02 | prison optically that glutamate will bind to glutamate receptors that are receptor channels and |
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| 06:10 | lawful influx of sodium. They're also to be permissible to both sodium and |
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| 06:15 | as you learn later. Next lecture this will influx of sodium positive charge |
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| 06:22 | cause a deep polarization of the possible and in the form of a predatory |
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| 06:26 | after potential. On the other if this neuron contains gabba release of |
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| 06:36 | and binding of Gaba, two Gaba in particular receptor subtype a gaba receptor |
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| 06:45 | will result in opening of the receptor the flux of fluoride into the |
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| 06:52 | the movement of negative and I on charged ion into the South will cause |
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| 07:00 | polarization. And this hyper polarization is inhibitory bus synaptic potential. So just |
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| 07:07 | with the PS PC PSP is also and depending on how many inhibitory synapses |
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| 07:15 | been activated that I PSP can be from half a million vault of hyper |
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| 07:20 | to 10 million volts of hyper polarization uh uh we learn more details about |
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| 07:29 | turn inhibitor signaling. In fact next . But uh if you're wondering what |
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| 07:41 | I'm covering, it's if you look your course content and you go through |
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| 07:50 | lecture notes, it's a neuro transmission neurotransmitter systems. So these are the |
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| 08:03 | lectures just to place you if you're where you are that we're covering? |
|
| 08:09 | huh. So direct versus indirect near we already alluded to it. This |
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| 08:16 | direct meaning that when a ligand or binds to a receptor, that receptor |
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| 08:22 | also a channel. So that receptor is a channel and can directly conduct |
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| 08:28 | inside outside the cell and so And indirect transmission. Otherwise referred to |
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| 08:36 | memorable tropic transmission. You have activation the receptor by neurotransmitter or chemical or |
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| 08:46 | but that receptor that receives a Lagan is not a channel. Instead |
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| 08:52 | is linked to the G protein complex activation of the G protein complex can |
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| 08:58 | regulate the opening and closing of the channels. And so these channels are |
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| 09:03 | to as g protein gated ion channels their key to open and closing them |
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| 09:12 | the G protein complex. So that never opens the receptor channel. But |
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| 09:19 | intracellular lee activates this complex. The that gets activated into cellular can also |
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| 09:28 | regulate the amounts of enzymes that are secondary messengers to influence the secondary messenger |
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| 09:39 | for different organize including for the nucleus and the transcription factors in the nucleus |
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| 09:47 | neurotransmitter different effect in the same You will see that in the in |
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| 09:55 | in a way there's certain receptors that bind the same neurotransmitter glutamate or they |
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| 10:04 | buy the single polling and two receptors mind that same substance that can be |
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| 10:12 | receptors. It can be norepinephrine They're going to be exerting opposing actions |
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| 10:18 | the cell. It can be one be de polarizing another one can be |
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| 10:23 | polarizing. If you talk about metabolic signaling, one could be stimulating protein |
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| 10:30 | that stimulates stimulatory gs increasing the production something and another one receptor that receives |
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| 10:37 | same molecule that a different subtype of linked to a different function differently program |
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| 10:44 | is inhibitory and that will drive down production of that same molecule enzyme chemical |
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| 10:52 | neurotransmitter, different effects on different So the same neurotransmitter and have a |
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| 10:59 | effect on one side. It can excited turn another salad can be |
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| 11:04 | This all speaks to what we discussed lecture that the response of the cell |
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| 11:10 | not depend on the chemical as much on the receptor and what that receptor |
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| 11:16 | whether it's a receptor channel whether it's g protein coupled receptor, your transmitter |
|
| 11:23 | . We started talking about acetylcholine and we're going to learn about the synthesis |
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| 11:30 | breakdown of the city of kobane of acetylcholine is in motor neurons, neuromuscular |
|
| 11:37 | you there's packs of acetylcholine molecules to produced in the pre frontal lobe |
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| 11:45 | prefrontal cortex and in brain standard for as well as you will see. |
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| 11:54 | peripheral nervous system, pre embryonic parasympathetic and in the brain you will see |
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| 12:00 | it is synthesized and we will come to the discussion that we already talked |
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| 12:06 | when I said that amino acids neurotransmitters as glutamate and Gaba a widely expressed |
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| 12:12 | neurons in different parts of the But these other substances means single coding |
|
| 12:21 | indifferent to have very specialized nuclei bunches cells that express them and then send |
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| 12:28 | signal through their axonal projections throughout the . So settle Colin gets synthesized when |
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| 12:36 | seal kolej and Colleen come together and . Kalina Siegel transfer is abbreviation is |
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| 12:46 | so they have to come together and . It produces settle Colleen that acetylcholine |
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| 12:53 | transported so you have the secular civil transporters, it will upload a single |
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| 12:58 | into the vesicles. Now the seal is going to get released. There's |
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| 13:04 | acetylcholine receptors that are shown here, optical one that is a receptor channel |
|
| 13:10 | that is our nicotine acetylcholine receptor and come back to it and a few |
|
| 13:15 | again and next it is acetylcholine which most sarinic receptor that is not a |
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| 13:21 | but instead it's G protein coupled So once the ceo Colin is released |
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| 13:28 | will buy into these receptors whatever receptors mathematically maybe expressed on specific neuronal subtypes |
|
| 13:37 | the remainder of the societal Colleen and general it's not just going to stay |
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| 13:42 | linger instead in the synaptic cleft that's to get broken down by a civil |
|
| 13:51 | a race okay, A C H N is abbreviation here for a single |
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| 13:56 | nurseries. So sick local investors will down a single Colin into acetic |
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| 14:02 | CH three C O. H. Colleen molecule. And then Colin molecule |
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| 14:09 | be transported back through the sodium co into the pre synaptic cell. Where |
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| 14:17 | Colin and acetyl coa a are going come together again and chat, they |
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| 14:23 | form a new is still coming molecule then acetylcholine will go through the same |
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| 14:28 | of being uploaded into vesicles release binding the respective receptors. Degrade advising local |
|
| 14:35 | estrus. Re uptake in this mechanism called re uptake. We have taken |
|
| 14:42 | into the personal topic terminals, re , reloaded, released exercise doses and |
|
| 14:51 | on. No, if you I told you earlier in the |
|
| 14:59 | maybe you have a page for a that you spared for Alzheimer's disease. |
|
| 15:07 | early in the semester we learned about of the pathology, like gross anatomical |
|
| 15:14 | Alzheimer's disease. Some of the things symptoms, we learned some of the |
|
| 15:18 | about hallmarks of pathology of Alzheimer's disease one of the things that we alluded |
|
| 15:27 | , we've never talked about is that Alzheimer's disease as a seal Colin |
|
| 15:33 | Colin ergic signaling. Sometimes people refer this core energetic tone and the brain |
|
| 15:40 | decreasing in the cns and these you learn in a few slides where |
|
| 15:48 | located. These neurons start dying early as you haven't answered about somehow these |
|
| 15:59 | ergic neurons are vulnerable to this early pathology and Alzheimer's disease. So one |
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| 16:11 | the uh main treatment of Alzheimer's Alzheimer's medications the target a civil pulling |
|
| 16:21 | race and in particular their a Seattle to race blockers or inhibitors. And |
|
| 16:31 | will even see some of the commercials will say since C. I. |
|
| 16:37 | . Because there might be some drug drug interactions. So if you watch |
|
| 16:41 | . V. At the airport or you watch Tv you see something, |
|
| 16:45 | sure you using sense of your own usually for elderly people if they're taking |
|
| 16:51 | medication. So Colin nestor is C . I am. That's how the |
|
| 16:58 | comes you know but there are some ministries inhibitors. There is one medication |
|
| 17:04 | there's Memon team that is targeting glutamate receptors but most of the multibillion dollar |
|
| 17:13 | industry is focused on this approach here on the market. And what does |
|
| 17:19 | do if you block a silicone erase this, prolongs the availability by |
|
| 17:28 | of a single Conan in the synoptic . That means that the civil Colin |
|
| 17:34 | gets released doesn't get degraded as easily on the dosage. Is that is |
|
| 17:43 | good solution. Only if you have single Colin neurons and only if those |
|
| 17:50 | still have a some acetylcholine and that not a great solution if these are |
|
| 17:59 | coming neurons. Our neuro degenerating or why because they can no longer produce |
|
| 18:12 | and if you're putting a saddle Colin is inhibitor in the absence but these |
|
| 18:19 | you may be putting it in the of a suitable clothing. So this |
|
| 18:25 | an important mechanism of action of Alzheimer's . You should add to your notes |
|
| 18:32 | it's not a cure, there is cure for Alzheimer's disease. It only |
|
| 18:39 | down the progression of the disease because early pathologies in the early breakdown of |
|
| 18:49 | arctic signaling will inevitably influence the neurons, nuclei and brain regions that |
|
| 18:58 | interconnected that are dependent on the seat Colin, normal tone in order to |
|
| 19:07 | normal functions, cognitive functions, sensory and so on. So this code |
|
| 19:18 | as you'll see pharmacologically could potentially be avenue of manipulation and it is seen |
|
| 19:26 | other means. But in general there's real need and Alzheimer's as you guys |
|
| 19:34 | interested in neuroscience and engineering and biology your pharmacology, there's a real need |
|
| 19:42 | in developing unique approaches and somehow preserving Seattle Colin signaling, busting the |
|
| 19:53 | untangling the tangles, so regulating the protein expression inside the cells regulating the |
|
| 20:03 | . P. P. L. . Apple protean expression unfolding outside the |
|
| 20:07 | the plaque formation. All of these also actually viable therapeutic approaches and some |
|
| 20:15 | them such as flag busting is quite big deal in the Euro pharmacological |
|
| 20:21 | Can you basically create substances that will bind to the plaques and somehow will |
|
| 20:29 | like bust up those plaques and those will just get digested by micro |
|
| 20:35 | So can you do both? You , bust the plaque, reactivate the |
|
| 20:39 | glia and can you control the microbial ? Because if you over activate leah |
|
| 20:47 | these processes glia gets also unchecked, it starts creating scars and it starts |
|
| 20:53 | more of cytokines that if you're creating information rather than reducing it, there's |
|
| 21:00 | fun balance there someplace there are two . I think you have to have |
|
| 21:03 | person. Yeah, why not? while? How do you give somebody |
|
| 21:16 | single company and in the brain it's a disease. Mhm. No, |
|
| 21:23 | that is an excellent question because it goes in the digestion. Then |
|
| 21:28 | have to wonder it passes in the . Doesn't get picked up. How |
|
| 21:33 | is the molecule? Right. Does cross the blood brain barrier? |
|
| 21:41 | Thank you injection. Okay, so get back to that also because you |
|
| 21:48 | want a specific site for injection. that's also a good question. And |
|
| 21:53 | this is also an opportunity given these networks like I mean networks and their |
|
| 21:59 | expression to limited parts of the brain opposed to glutamate or gaba which is |
|
| 22:05 | over cortex and hippocampus and brainstem and on. So Hang on to that |
|
| 22:14 | . I think it's very controversial. that patients without I think patients I |
|
| 22:26 | Alzheimer's cannot have Emily burns but still a and I guess what the process |
|
| 22:32 | a very good question. Uh The here, one of the students mentioned |
|
| 22:41 | study and amyloid plaques and the drug is controversial is the approved because Alzheimer's |
|
| 22:48 | have symptoms without having the plaques. I think the most and the best |
|
| 22:55 | action is to have the ability to the presence of plaques and you can |
|
| 23:00 | that with blood markers and you can that was imaging but advanced stages and |
|
| 23:10 | not sure. Maybe you can look if you're interested in the new stuff |
|
| 23:14 | Alzheimer's disease, if there is a human marker for the plaques and the |
|
| 23:23 | , who can be images of living ? I don't know. But I |
|
| 23:29 | that there are blood markers have been least indicate and suggest. And of |
|
| 23:35 | in severe Alzheimer's pathologies and maybe this where it's most applicable. The plug |
|
| 23:42 | if it is so severe that you see on CT scan. But something |
|
| 23:49 | which would indicate formation of really large and scarring tissue around them. Maybe |
|
| 23:57 | what's for as a I would probably as advanced stages of Alzheimer's disease where |
|
| 24:06 | plaques are causing a lot of loss function. I think politics like I |
|
| 24:24 | there's always politics. There's always something involved and there's always interest for both |
|
| 24:32 | and profit. You know. So . Yeah, because I don't find |
|
| 24:47 | this important therapy only useful. Yes. Yeah. But in the |
|
| 25:01 | of any alternative is usually increase of that happens early onset, low concentration |
|
| 25:08 | you progress with the disease and concentration the drug may be increased by a |
|
| 25:13 | too. And at first it may just barely regulating that amount of the |
|
| 25:19 | code or even later increases the regulation that amount, allowing for more subtle |
|
| 25:24 | . And so but most of the drugs, as you know, everything |
|
| 25:29 | you're taking is not only affecting your , expecting your liver, your |
|
| 25:34 | your other portions uh and the not just in the cns. And |
|
| 25:40 | there's a burden is a burden on body for taking the drugs to not |
|
| 25:48 | their beauty burden, but just Move things like that. So all |
|
| 25:55 | . Kind of. Well, if I don't have much time to discuss |
|
| 26:07 | , but if you look up it's to the top road in there's two |
|
| 26:13 | kind of protein systems that are upset Alzheimer's disease. And I wish I |
|
| 26:17 | a slide. I could show you quickly. But we know what |
|
| 26:25 | But we don't have a very good of approaching and therapeutical. So with |
|
| 26:30 | mechanisms we know pretty well behind No. Uh I'll see if I |
|
| 26:35 | find the slide. Maybe that will a little bit of that for the |
|
| 26:39 | next lecture or so. Very good . Thank you guys I'm gonna move |
|
| 26:45 | a little bit and talk about Acetylcholine as we talked about combined two |
|
| 26:55 | channel, that receptor channel is called receptor because nicotine will also bind to |
|
| 27:02 | receptor. So nicotine will buy into receptor, it will open the receptor |
|
| 27:09 | and by opening the receptor channel it as an agonist on an activator of |
|
| 27:17 | receptor? Oh the continent receptor also its own antagonist. So this is |
|
| 27:24 | ira and what you're learning is common neuro pharmacology. How do different substances |
|
| 27:32 | and close the channels? And acetylcholine course is an agonist is a natural |
|
| 27:41 | for both the Continent receptor and masculinity . That means that will initiate the |
|
| 27:48 | of both the receptor channel and the G protein complex, musk. Corinne |
|
| 27:56 | a separate agonist and that's what it's must heretic receptors. So you can |
|
| 28:01 | these receptors pharmacological E one will be to nicotine. Another one's mustering what |
|
| 28:06 | won't be responsive or blocked by chara a trippin will inhibit the activation of |
|
| 28:15 | . Nick receptor. So a trumpian antagonist here. Uh huh. And |
|
| 28:30 | you recall last time we talked about systems and I think that in this |
|
| 28:38 | this in this uh case I want switch to a different slide. Uh |
|
| 28:47 | . Mhm. Wait a second. and in this slide what is illustrated |
|
| 28:59 | how do you determine where different neurotransmitter . Remember what the neurotransmitter system is |
|
| 29:06 | neurotransmitter synthesizing ends on can be a enzyme that degrades it degrading ends on |
|
| 29:15 | be a specific transporter. Uh All these things are part of the, |
|
| 29:22 | of the system, bicycle, It's of the neurotransmitter system. So you |
|
| 29:29 | determine where your neurotransmitter systems, record components are located such as neurotransmitters such |
|
| 29:37 | receptors the most common way to do in the lab. And this can |
|
| 29:42 | done in the human tissue to and is done in the clinic after you |
|
| 29:46 | human tissue or cancer. It's not specific and do immune, artistic chemistry |
|
| 29:52 | liver tissues. Can tissue to determine markers or what specific molecules are expressed |
|
| 29:58 | over expressed. There's high levels of molecules are under express low levels of |
|
| 30:04 | molecules. So um you know history essentially utilizes antibodies and antibodies that you |
|
| 30:12 | take from one animal such as mouse rat and injected into rabbit like a |
|
| 30:21 | and the animal will create an antibody isolate this antibody this black white and |
|
| 30:28 | can tag the anti body with a marker and that visible marker could be |
|
| 30:36 | it's immunities to chemistry currently is done fluorescence. So these markets are fluorescent |
|
| 30:42 | means that they will exude, lied a certain wavelength and you can use |
|
| 30:52 | markers and different wavelengths of fluorescent and can do multiple immuno history chemical marker |
|
| 31:00 | on the same tissue or the same as long as they bind to different |
|
| 31:06 | say one is binding to the another is binding to receptors. Another |
|
| 31:10 | is binding to synthesizing enzyme and you to see all three of them. |
|
| 31:15 | you will tag them with three different markers and then the microscope you will |
|
| 31:21 | the fluorescent microscope you will switch the to pick up just the red, |
|
| 31:27 | the green or just the yellow color is a different marker and you will |
|
| 31:33 | where different aspects of this neurotransmitter systems located. You can take these tagged |
|
| 31:42 | antibodies and apply them onto the tissue then the immuno history chemistry preparations a |
|
| 31:49 | of times of course and it's only vitro where this is done a lot |
|
| 31:56 | times you will be doing things like , putting the tissue on the shaker |
|
| 32:01 | the shaking table. You may be it through the steps where you're applying |
|
| 32:06 | little bit of detergent which will open the plasma membrane and allow for certain |
|
| 32:13 | to enter into the South. And antibodies that are specific to this neurotransmitter |
|
| 32:20 | is green neurotransmitter. We'll enter into south that will have this green block |
|
| 32:26 | will bind to these cells. And as a part of the immunity chemistry |
|
| 32:30 | you will go through multiple steps of and even if the antibodies penetrate into |
|
| 32:37 | nearby south and the plasma membrane during washing stop, they will get washed |
|
| 32:44 | . Only the ones that are truly to the molecule of interest such as |
|
| 32:52 | will then show up under a microscope one cell will glow and yellow. |
|
| 32:58 | the next door cell that does not that near transmitter will not show any |
|
| 33:04 | signal. You can use immuno history and immuno fluorescence to tag uh |
|
| 33:16 | You can tag neurotransmitters. You can individual synapses still by using in United |
|
| 33:25 | chemistry for very specific molecules. You distinguish between different set types of |
|
| 33:31 | There's microbrewery a specific in una has chemistry that you can perform and visualize |
|
| 33:37 | of the micro glial south. That's very useful tool because you can combine |
|
| 33:42 | with other things too. Now the tool that is used to find these |
|
| 33:48 | is in situ hybridization and in this the radioactively labelled probe with the proper |
|
| 33:56 | of complementary new clegg assets. this is something that you can |
|
| 34:03 | you can design a sequence of nucleic because it's supposed economic error. So |
|
| 34:09 | know what this sequence will pull it . You can go on find it |
|
| 34:13 | the gene engines and jean searches called Wiebe some attitude. We'll give you |
|
| 34:21 | cost you know $10, whatever radioactively tag. And then you can target |
|
| 34:30 | specific strand of messenger RNA. So of hybridization does not go for proved |
|
| 34:38 | does not go for molecule but rather RNA what it codes for. That's |
|
| 34:45 | the message is love data and it radioactive label. And similarly to in |
|
| 34:52 | know chemistry only the cells that have complementary sequence to the sequence that you've |
|
| 35:01 | and applied onto petition only those cells show the radioactive marker. And it's |
|
| 35:10 | just uh you know, it's a view to look at individual networks, |
|
| 35:16 | cells using these techniques. But on ride here is an example of a |
|
| 35:24 | embryo in the early development and wherever seeing this dark blue color and you're |
|
| 35:32 | seeing it everywhere. This is the . So you're not seeing much of |
|
| 35:36 | in the stomach, You're not seeing in the legs. You're seeing it |
|
| 35:41 | the spinal cord. You're singing going into into the brain stem, |
|
| 35:47 | not seeing much of it here and , upper cortical regions. And in |
|
| 35:53 | this substance here is tyrosine kind is and it's not important to know for |
|
| 36:01 | . But it is important to know these techniques and you know, his |
|
| 36:05 | chemistry and zero hybridization can give you aerial view and the expression of the |
|
| 36:13 | of neurotransmitter systems may change with development change with age. Obviously obviously they |
|
| 36:23 | pathology as well. A third technique is functional more functional because here you're |
|
| 36:30 | a static imaging with functionally from the days when Otello we isolated, still |
|
| 36:37 | and applied it to an stimulated heart that stimulated heart slow down its |
|
| 36:43 | Once we had glutamate Gaba isolated North and all of these other neurotransmitters. |
|
| 36:50 | the means. We then started using in the lab Applying it on two |
|
| 36:57 | doing mimicry no transmitter or synoptic So you can stimulate a pre synaptic |
|
| 37:04 | that contains glutamate and it will release and it will cause a deep polarization |
|
| 37:09 | this neuron. Or you can isolate and put it inside the pipe pad |
|
| 37:15 | the liquid and release this glue to onto the gun rights and the response |
|
| 37:22 | the cell we're recording from should be . It should also be an excitatory |
|
| 37:28 | synaptic potential. Mrs glue, dermatologic or you apply glue to make and |
|
| 37:34 | my previous lecture alluded to an article is in the lecture supporting materials on |
|
| 37:40 | caging of neurotransmitters? It's important that think about this for a second. |
|
| 37:48 | what happens if you push this fluid of the pipette and you're trying to |
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| 37:54 | this very small region here on the . Are you going to be exclusively |
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| 38:00 | in doing so when the surrounding environment a Prius. No so this substance |
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| 38:06 | going to follow the law of That means that there's going to be |
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| 38:11 | concentration of the substance of the synapse interest slightly lower in the surrounding synopsis |
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| 38:17 | as further as it goes is it to the essentially negligible concentration uh |
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| 38:27 | not a very accurate way. In outlet way. And so what the |
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| 38:33 | allows to do, it allows you actually cage these neurotransmitters and I'll you |
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| 38:40 | cage glutamine, we can cage gather then use microscope blazers to activate an |
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| 38:49 | blue tonight at one single dendritic Now it's very precise signs and microscopy |
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| 38:56 | laser microscopy is very fast. The are now going down to mental second |
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| 39:04 | but in any case nanosecond you can this very fast within nanoseconds or |
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| 39:12 | You can activate several precise and it in just one or two or three |
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| 39:19 | of interest. So that's why this technique uh until the we discovered this |
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| 39:26 | 100 years ago it is 100 year technique. We just improved the microscopes |
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| 39:32 | the ability to count to single neurons them rights and stimulate them in this |
|
| 39:39 | like diffuse fashion, knows a lot science that was done A lot of |
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| 39:43 | that were done using this technique. now moving into the 21st century I |
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| 39:48 | these laser microscopy techniques engaging of neurotransmitters getting to very single synapse of every |
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| 39:56 | molecule within the synapse and the very fashion and across states. So that |
|
| 40:03 | is uh where the science is having days. Okay, remember we talked |
|
| 40:10 | amino acids and groups of the In fact we had this slide that |
|
| 40:18 | . I uh inserted in addition to . You know acids the means and |
|
| 40:25 | ties. And they said no you're responsible to learn all of the breakdown |
|
| 40:29 | synthesis. Except for the things that really stress. Like casino calling. |
|
| 40:34 | huh. For other things that we about gamma wait a minute. But |
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| 40:39 | will not talk about dying Norfolk. I'll never ask. You wouldn't die |
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| 40:43 | and as a precursor to or how is synthesized and so on. |
|
| 40:48 | We mentioned these very interesting classes of that are gases which is not just |
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| 40:54 | and carbon monoxide. You learn more them today as well as endocannabinoid. |
|
| 40:59 | the function differently than not stored in . It also mostly exert their effects |
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| 41:06 | the priests unethically located receptors. ATP then isn't dry, phosphate and a |
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| 41:13 | in the core of the ATP molecule very interesting. Uh neurotransmitter neurotransmitter systems |
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| 41:21 | I will be mentioning in this course well. Okay, so what else |
|
| 41:26 | interesting in the slide Galba t. glittery glue them in. We dominates |
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| 41:36 | blue linked. So if you have I mean you can make good |
|
| 41:41 | So all of the excited ourselves. have good families If you have |
|
| 41:49 | Guess what else he can do? can produce gaba. So this is |
|
| 41:57 | yeah. I'm I'm you know beauty car box pallets or God. And |
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| 42:03 | of the inhibitory neurons will contain All right, Where did they get |
|
| 42:10 | from? Mhm. They don't express a minute. Where do they get |
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| 42:17 | from? If you don't make will ? Where how do you get it |
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| 42:22 | you don't make it? And you say you imported from Canada Mexico china |
|
| 42:32 | . Right? So you you have transporter probably um a transporter or another |
|
| 42:43 | to get you the glutamate to make into Gabba but all of the neurons |
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| 42:49 | inhibit their neurons. You want to them? Not for glutamate. I |
|
| 42:54 | to send them for God. Okay Tommy casa dicker boxers a single |
|
| 43:01 | This is our pathway with a chat also know that pathway with a breakdown |
|
| 43:06 | the local investor is serotonin trip to . Trip to Faneuil through review some |
|
| 43:15 | this popular too. The trip to which a lot of you if you |
|
| 43:20 | thanksgiving with a turkey, he had big dose of took the fan which |
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| 43:25 | rich in Turkey and that is a to your happy serotonin molecule which is |
|
| 43:31 | hydroxy took to me in five htp . No, there's a lot of |
|
| 43:38 | interesting things. Tyrosine will make dopa dopa die hydroxy Federal Lauerman. Aldo |
|
| 43:45 | a precursor for dopamine. Dopamine is precursor for nor epinephrine, norepinephrine is |
|
| 43:51 | . Epinephrine. All of these different do different things and they expressed |
|
| 43:59 | So as we talked about the not mediate different functions. If you have |
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| 44:06 | dysfunction in acetylcholine and Colin ergic neurons its associated with Alzheimer's disease. A |
|
| 44:14 | and dopamine signaling is associated with motor , the general disorders such as Parkinson's |
|
| 44:22 | . Okay, if you're talking about like a dennison, who said that |
|
| 44:27 | rise and they help you relax and asleep. You talk about molecules that |
|
| 44:32 | and norepinephrine epinephrine. It's something that and engages, right? So just |
|
| 44:39 | other it's an active upstate instead of this is the pharmacology that we already |
|
| 44:48 | and this is the pharmacology that we know also like a technical mascara. |
|
| 44:57 | review a little bit more about the proteins in particular g proteins have what |
|
| 45:03 | discussed the short good pathway. The pathways refer to this right here. |
|
| 45:11 | what is most koranic, acetylcholine receptor and when this this shortage catholic when |
|
| 45:19 | civil coming binds to Moscow clinic receptor the do protein? The data gamma |
|
| 45:25 | of the spread in will then but essentially from this complex and it will |
|
| 45:33 | and will bind to the nearby potassium binding of this jeopardy in complex subunit |
|
| 45:41 | the potassium channels will open the potassium when you open the potassium channels, |
|
| 45:50 | is going to leave the south the charge leaving the south so binding a |
|
| 45:58 | Colleen the most horrific receptor metal tropic clearly perceptible open the potassium channel potassium |
|
| 46:06 | leave the cell and the result is to be hyper polarization, potassium positive |
|
| 46:15 | leaving the sound making the inside more . You continue. Acetylcholine receptor allows |
|
| 46:22 | influx of sodium and it's deep polarizing neurons. Most quranic is hyper polarizing |
|
| 46:30 | and they can co express both. then it depends where it is located |
|
| 46:36 | early. What networks are dominated by receptors? What cells are dominated more |
|
| 46:42 | what receptors and they're also subtypes of nicotine thick and muscular receptors. There's |
|
| 46:47 | just 1 -1 hispanic receptors slightly different . Splice variants if you make these |
|
| 46:55 | that are functional normal splice variants Yeah let's look at the glutamate cycle |
|
| 47:05 | let's talk about what is happening in brain. In general neurons communicate with |
|
| 47:11 | neurons but they do that. You what we call a tri apartheid synapse |
|
| 47:19 | apartheid synapses. You're on Guam neuron who is an optic girl. Our |
|
| 47:29 | neuron and we also and in this in particular disastrous site. So we |
|
| 47:35 | about astrocytes and we said that all are their household chores and they have |
|
| 47:41 | blood brain barrier a lot of supportive . But this is an example of |
|
| 47:47 | intricately clear control neuronal synaptic transmission glue has produced synthesized from glued mm and |
|
| 47:58 | theirselves with blue dominates and ATP and uploaded into the vesicles. When glutamate |
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| 48:06 | released. This is the subject of following electrical intimate also binds to a |
|
| 48:13 | channels that are on a tropical intimate . And the D. A. |
|
| 48:18 | chicken. We learn about these. then they can also bind the metabolic |
|
| 48:22 | ornamental stoppage. And there's at least 12 different subtypes of metal with tropical |
|
| 48:27 | a major stuff. And those receptors will have typically an opposing action where |
|
| 48:36 | binding to Iowa tropic receptor will cause attic deep polarization binding to medical tropic |
|
| 48:44 | can actually cause a hyper realistic. some instances it can enhance the polarization |
|
| 48:51 | some instances can actually do the So this goes back to what we |
|
| 48:57 | a few slides again the same substance receptor, nicotine ECB you polarization must |
|
| 49:03 | hyper polarization. Two different receptors, same substance, different outcome for the |
|
| 49:08 | functional outcome. This glutamate when it's the synoptic collapse it doesn't linger here |
|
| 49:14 | lot. It gets transported back neuronal re uploaded into the vesicles and we |
|
| 49:23 | again. But a portion of this important the most important excited to a |
|
| 49:30 | is transported through real rhythm. A and it's turned through terminates enters into |
|
| 49:40 | and then that blew them in is back or transported exits out, released |
|
| 49:47 | gets transported into the neurons where it with the terminus synthesizing to glutamate glutamine |
|
| 49:58 | the time of Cassidy is acidic Sorry it's a it's a it's a |
|
| 50:04 | gloomy. Okay so atomic acid is and released again and now you can |
|
| 50:13 | that those two neurons and Glia both an intricate role in the overall |
|
| 50:21 | A little mint. So Glia can how much of this excited are. |
|
| 50:27 | transmission can take place between two neurons it is responsible for cycling. Part |
|
| 50:34 | that glutamine glutamate is turning into the and recycling it back into europe. |
|
| 50:43 | this is not just for probably a recycling not just for excited neurons but |
|
| 50:49 | for inhibitor announced to it's uh cycling Gaba and re update of Gaba. |
|
| 50:58 | china cola means and most of the are now going to be on the |
|
| 51:06 | . But I want you to pay of how things are made in the |
|
| 51:09 | . If you're not familiar merger with biochemistry, tyrosine will have hydroxy |
|
| 51:16 | What is hydroxy liss? It's a group. Ohr so don't don't don't |
|
| 51:26 | confused or don't think that biochemistry is . So lost now. So you |
|
| 51:35 | hydroxy lists of uh oh age, have Kobach Selous car box Eliza seal |
|
| 51:44 | in the southern enzymes that are deco oasis. Then they take the ceo |
|
| 51:52 | off the G carb oxalate. They this Citigroup and another one comes in |
|
| 51:59 | the hydroxy silicates. ADR oscillates another here. Another one commence and it's |
|
| 52:08 | ethel and transfers. So the method besieged there europe. So these are |
|
| 52:16 | of your major changes and bio synthesis uh and somatic changes in regulation that |
|
| 52:24 | happening. Hydroxy elation, deacon of in isolation. Mhm. We'll also |
|
| 52:32 | a little bit about foster relation. defense for relation. I've been waiting |
|
| 52:38 | a biochemistry Iraq song by famous rap but it hasn't come about yet. |
|
| 52:48 | cata cola means all of these We're talking about dopamine, norepinephrine and |
|
| 52:54 | upstate movement, mood, good attention but also this is all |
|
| 53:00 | So all of these molecules are expressed the periphery, not just in the |
|
| 53:04 | to cata colonies will go through the cycle and they will be re uptake |
|
| 53:10 | back and catch a colony. And is controlled by amphetamines and cocaine. |
|
| 53:17 | it can be controlled in a therapeutic pharmacological drug like fashion. But obviously |
|
| 53:23 | is also abused with illicit drugs such cocaine. And so the function of |
|
| 53:29 | has prolonged the by availability availability of Colombians which are uppers mood enhancers if |
|
| 53:39 | may is something that activates your And so it's something that is quite |
|
| 53:47 | and has been on the market and been synthesized not only produced from the |
|
| 53:57 | cocaine comes from cocoa plants. If can imagine some crusty dude someplace. |
|
| 54:05 | a broken down house trying to put together. Make some powder and mix |
|
| 54:12 | powder with something else and stuff. and some pliers and floated across the |
|
| 54:18 | into the United States or something like . You know. So uh and |
|
| 54:25 | now actually we talked about it a bit when we talk about the cannabinoids |
|
| 54:31 | it's very important because there's a huge of synthetic opioids. We have not |
|
| 54:39 | uh pandemic but we also have Opioid, epidemic synthetic drug epidemic stuff |
|
| 54:51 | seems to be legal but it's even laura unknown or not really legal. |
|
| 55:01 | pay attention to these things but the of action is a lot of it |
|
| 55:06 | through the update. Also pay attention serotonin smooth appetite sweep learning bad |
|
| 55:15 | no appetite, no sleep, bad . It's all interrelated. Right? |
|
| 55:22 | it's this cycle here. Your trip fan cycle. And if you look |
|
| 55:27 | PROzac it's most common brand name. tied depressant drug. A lot of |
|
| 55:32 | may have heard is like I said antidepressant because serotonin is happy mood. |
|
| 55:40 | if you blocked me uptake of what are you doing? You prolonging |
|
| 55:45 | by availability of serotonin in the synoptic . Mm. So now you have |
|
| 55:52 | of some interesting your pharmacological approaches. can manipulate the re uptake of molecules |
|
| 56:02 | you can manipulate the breakdown of Yeah. L dopa for example is |
|
| 56:09 | precursor for dopamine and L dopa is and you need to increase dopamine production |
|
| 56:18 | a drug that is L dopa. this is another approach, You increase |
|
| 56:24 | presence of the precursor. So maybe cannot inject the saddle Colleen into specific |
|
| 56:33 | of the brain or feed people a Colin. But maybe there's also a |
|
| 56:39 | to find molecules that of precursors or mimic the activity of the naturally produced |
|
| 56:49 | such as steel Colin. But how you get there? How do you |
|
| 56:52 | them? Not only the brave within synapses, mm. Now, g |
|
| 56:59 | in addition to most of these simians will have G proteins and some of |
|
| 57:06 | uh such as norepinephrine will function exclusively the G protein linked cascades and g |
|
| 57:13 | cascades is not only something that you affect through shortcut, halfway nearby ion |
|
| 57:20 | . Open or close these iron you can also activate downstream numbering bound |
|
| 57:26 | santa. Solich enzymes you can affect chemical reactions and you can activate or |
|
| 57:35 | downstream enzyme creation. Pyrenees hospitals all way down to the prescription factors in |
|
| 57:41 | nucleus. So all the way from receptor in the num brain If the |
|
| 57:47 | and the message is conveyed in the way in a proper way, it |
|
| 57:52 | actually lead you all the way to gene expression of. Okay, this |
|
| 58:00 | a norepinephrine, Norepinephrine is another example it's a great example what we call |
|
| 58:07 | pull mechanisms where when norepinephrine binds the receptor. This beta receptor. Unfortunately |
|
| 58:15 | blurred out as beta receptors linked to G protein or gs and binding of |
|
| 58:23 | to beta receptor who activate the Gs increase the production of a general |
|
| 58:30 | It will turn 80 P into cyclic and will produce a lot of protein |
|
| 58:35 | A or P. K. Highness's the south are responsible for phosphor relation |
|
| 58:43 | adding this P. 04 group. force for relating channels or defrost correlating |
|
| 58:49 | is a function of hospital basis. kindnesses appeal for foster to cIS. |
|
| 58:56 | . Phosphor really take the phosphate group and this balance of course formulating and |
|
| 59:03 | for leading the channels is very important regulating the receptor channels and ion channels |
|
| 59:10 | regulating downstream secondary messenger cascades. So the same molecule binds to alpha two |
|
| 59:18 | and alpha two receptors linked to inhibitory stimulatory and inhibitory G protein G. |
|
| 59:25 | . The function of the G. to inhibit a general cyclist function and |
|
| 59:33 | the amount of psycho campion, reduce amount of protein kind they say |
|
| 59:39 | Now you can imagine this massive neuron that has all of these receptors |
|
| 59:46 | Some of them could be located next each other, some of them farther |
|
| 59:50 | away. One of them is pushing system to produce more cycling camping including |
|
| 59:56 | . A another one is inhibiting or away from making more cycling campy more |
|
| 60:04 | eggs. So you have these spatial of these neurotransmitters. The molecules get |
|
| 60:11 | and binds to the receptors. Through jeopardy in a couple of cascades is |
|
| 60:15 | cellular regulation of Pioneer systems hospitals is balance of these kind of cases and |
|
| 60:21 | possible relation and defaults for relation of channel and affects all the way into |
|
| 60:27 | transcription factors inside there itself. Now is what I talked about earlier this |
|
| 60:38 | , we'll put a lot of things perspective Now norepinephrine is not produced in |
|
| 60:46 | and it is not produced in the cortex and this is not produced in |
|
| 60:52 | sarah dour glutamate is Jabba is, all over. You'll find excitatory glutamate |
|
| 61:02 | . Salento hit the campus and the lobe you'll find occipital, parietal |
|
| 61:08 | frontal lobe. Everyone. So their as you saw by neurons. Very |
|
| 61:15 | so ubiquitously throughout different brain structures. is not the case for a |
|
| 61:22 | There's an european african and the nucleus produces norepinephrine is locust civilians right? |
|
| 61:30 | blue nucleus the blue locus focuses site is a collection of South that is |
|
| 61:37 | for the same or similar function. this function of this nucleus of local |
|
| 61:43 | . It sounds like a gladiator saying be a movie name. Look civilians |
|
| 61:50 | serious will release norepinephrine through its projections these projections are wide and far. |
|
| 61:58 | so these arrows indicate all of the throughout the cortex and cerebellum and even |
|
| 62:04 | the spinal cord where norepinephrine is going go through. It will have external |
|
| 62:12 | from these brainstem nuclei odd that will lee innovate. The cortex. Sub |
|
| 62:19 | areas and spinal cord and cerebellum and were up enough and onto these |
|
| 62:25 | And so these neurons will then have author or two receptors. May be |
|
| 62:30 | . Maybe both. And this is a lot of times is referred to |
|
| 62:34 | a sprinkler system because there is no pathway. One specific ending to the |
|
| 62:42 | is going from here to argue with there and it stops rather it seems |
|
| 62:47 | just spread the love all throughout different circuits. Serotonin is produced by rafei |
|
| 62:59 | . And if you look at these rafei nuclei here, the sparkle rafei |
|
| 63:05 | will project into basil ganglia. Will into the cortex, frontal cortex exhibit |
|
| 63:11 | cortex will project them to the Same story. But you will not |
|
| 63:17 | a selling cerebellum that synthesizes serotonin. going to be synthesized in these very |
|
| 63:25 | nuclei in the brainstem and the wrath nuclear. The ones that are on |
|
| 63:30 | and purple. We'll send their projections the cortex and cerebellum. The ones |
|
| 63:36 | are shown in green. Well we'll their serotonin projections into the spinal cord |
|
| 63:44 | and then to the periphery. Does change a little bit. Your perspective |
|
| 63:53 | how you would want to have therapeutic to some of the neurological disorders that |
|
| 64:00 | actually need to target specific parts of brain. But when somebody takes a |
|
| 64:09 | , it only targets if you're talking a single Colin prolonging acetylcholine, right |
|
| 64:16 | look at a simple coding expression right in the green. You have magna |
|
| 64:20 | basal forebrain. My single program is and you have a silicone in particular |
|
| 64:29 | and lateral door. So take mental . That's it. It's not not |
|
| 64:37 | but you can see the projections out this house will go there broadly and |
|
| 64:42 | Colleen is dominating the prefrontal frontal cortex so lack of that will start affecting |
|
| 64:49 | functions. And if it's dominating the circus it will affect other functions. |
|
| 64:56 | frontal cortex, cognition, planning executive and then hippocampus it will start affecting |
|
| 65:06 | , emotions. All of these are be different things depending on the structures |
|
| 65:10 | they will have different receptors and they're in their own circuits inside the |
|
| 65:16 | So you can see the histamine is here to better monitor nucleus ventral take |
|
| 65:23 | area and substantial *** will produce So if you have dopamine dysfunction. |
|
| 65:31 | you're looking at a loss of cells dysfunction in the cells in this brain |
|
| 65:37 | but don't kill upon. Thine already about it local. Surely is already |
|
| 65:41 | about Iraqi nuclear. Already talked about serotonin. These are all their good |
|
| 65:46 | questions actually you know they are. finally we'll discuss linda cannabinoids. Okay |
|
| 65:55 | maybe we're pushing a little bit of here but it's very important that we |
|
| 66:01 | why we singled out. And the and why we actually singled out the |
|
| 66:08 | is not just oxide and carbon monoxide most of the things that we talked |
|
| 66:13 | this particular release crease line optically binding the fasten optic receptors and this is |
|
| 66:18 | we call interrogate signaling from prison object personal. And these molecules nitrous oxide |
|
| 66:26 | carbon monoxide and the cannabinoids. They're because they are not stored in the |
|
| 66:32 | . There are also different because in case of all of them. But |
|
| 66:35 | will use an example of endocannabinoid here there is a lot of activity in |
|
| 66:41 | glutamate or gaba. Ergic synapses. there is a lot of deep polarization |
|
| 66:46 | these pre synaptic neurons there's going to pasta Matic activation of influx of |
|
| 66:51 | Matic calcium which will turn on the of endocannabinoid boston optical, they're not |
|
| 66:58 | in the vesicles so they will travel the plasma membranes or lipid soluble. |
|
| 67:04 | under cannabinoids such as anandamide and two G to a abdominal glycerol. They |
|
| 67:11 | travel retro greatly and buying to the their receptors are located prison optically so |
|
| 67:18 | function is retrograde function in affecting the synaptic neurons. When under Cannavino is |
|
| 67:26 | two CB 1 receptors that are located neurons they're linked to G protein coupled |
|
| 67:34 | and they will control the calcium They will close the calcium channel recall |
|
| 67:39 | calcium influx and calcium channel activation is necessary thing for vesicular fusion a neurotransmitter |
|
| 67:49 | Therefore by retro greatly regulating CB one and the cannabinoids regulate the release of |
|
| 67:59 | and Gaba. Or they suppress the of glutamate and Gaba. And therefore |
|
| 68:06 | referred to as deep polarization induced suppression inhibition when there is a lot of |
|
| 68:11 | polarization prison optically. And this far neuron produces under cannabinoids. It will |
|
| 68:21 | greatly through CB one receptor activation suppress inhibition by suppressing the vesicular binding and |
|
| 68:30 | release. It can do that for excited to the synopsis to so deep |
|
| 68:36 | . Blue Dome eight. A lot calcium here and the cannabinoids binding to |
|
| 68:42 | juan closing calcium will regulate glutamate So and the cannabinoids in the brain |
|
| 68:50 | the NHL and cll nitrous oxide and monoxide. They have their respect the |
|
| 68:57 | on the pre synaptic terminals of neurons they travel retro greatly to pre synaptic |
|
| 69:04 | and regulates synaptic transmission to the G coupled receptors here. There's also CB |
|
| 69:12 | receptors. So we have a whole on under cannabinoid system. You're going |
|
| 69:15 | leave. They're smart knowing a lot things CB two receptors are predominantly expressed |
|
| 69:21 | Leo's health and in particular micro glial . And as I already mentioned earlier |
|
| 69:28 | one of the functions of microbial cells control of information and release of pro |
|
| 69:35 | cytokines You can think of CB one system it needs to be awoken with |
|
| 69:42 | lot of activity. Once it's awoken the cannabinoids through CB one receptor system |
|
| 69:48 | control fast neural transmission and will balance and inhibition and through binding to glia |
|
| 69:57 | two receptors. And the cannabinoids will slower processes such as grill functions, |
|
| 70:06 | functions, cytokine release. So again temporal scales. CB one receptor, |
|
| 70:14 | is also can be bound by THC tetrahydrocannabinol. Delta the ntc delta man |
|
| 70:25 | is a phyto cannabinoids. Andrew cannabinoids produced endogenous lee Fito produced by |
|
| 70:33 | THC is produced by plants and it will bind to CB one receptors. |
|
| 70:39 | will also buy into cannabinoid receptors to another function of CB one receptors is |
|
| 70:46 | only regulating this fast gabon glutamate synaptic , but by new york under cannabinoids |
|
| 70:55 | CB one receptors, Ananda is a . Sand script gives a good |
|
| 71:01 | This is the runner's high that is by the production of endocannabinoid. Is |
|
| 71:07 | ananda THC binding to CB one receptors various levels will cause ananda or |
|
| 71:16 | That is often referred to as the fact and some people will say psycho |
|
| 71:21 | intoxicating but the crack board is a effect of psychoactive effect is changing the |
|
| 71:29 | that your psyche is working and we talk about doping my etcetera. Had |
|
| 71:35 | hydrogen avenue and Canada's plant does not delta nine THC cannabis plant is not |
|
| 71:47 | in its raw green form it produces nine THC a the civic form of |
|
| 71:54 | THC which is non psychoactive non so eating raw green cannabis plant does |
|
| 72:03 | get one high. So THC a to be converted into THC delta nine |
|
| 72:12 | to be psychoactive. And that is by heating the plan. Typically cannabis |
|
| 72:18 | heating it, smoking it vaporizing it in the production process when it's being |
|
| 72:23 | , extracted and sold and shoes and on. But the plant itself is |
|
| 72:30 | innocent actually. I don't know why is being punished so much now. |
|
| 72:35 | needs to be reviewed and punished? maybe the guys down the street and |
|
| 72:40 | around selling delta eight THC. That's cautionary word again, don't bother with |
|
| 72:50 | stuff that is unknown. Delta eight a synthetic, is a semi synthetic |
|
| 72:58 | that is produced from a natural cannabinoid . So it doesn't come naturally in |
|
| 73:04 | plant and it's not naturally extracted from plant. But rather you have to |
|
| 73:09 | through a separate chemical processing to change double bond information between carbon eight and |
|
| 73:16 | versus carbon nine and 10 to move double bond to make it delta |
|
| 73:22 | There's a lot of stuff we don't about sending synthetic process. There is |
|
| 73:27 | enzyme in the plant that synthesizes Delta . There is no enzyme that synthesizes |
|
| 73:33 | nine. There's enzyme that synthesizes delta THC. A but there is no |
|
| 73:39 | eight THC a. That's how we it doesn't come from the planet. |
|
| 73:45 | , so these are all very interesting . I think that are very |
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| 73:49 | I'm going to stop here because I'm over time a little bit. Thank |
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| 73:52 | for being here. Have a great and I will see everyone on |
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| 73:58 | My apologies, but I have to out of the classroom. So if |
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| 74:01 | have any questions hold on to them also expect your exams to be released |
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| 74:08 | friday afternoon. Okay, So take of guys see you everyone on |
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