© Distribution of this video is restricted by its owner
Transcript ×
Auto highlight
Font-size
00:01 This is lecture 11 of neuroscience and time we talked about differences between amino

00:08 neurotransmitters and we said that those are broadly expressed throughout the brain and the

00:13 and sub cortical areas as well. talked about the means and we said

00:17 the means are very different in the that they are actually expressed in very

00:22 locations with nuclei in the brain and projections from these nuclei are diffused in

00:29 broad reaching so they will innovate a of cortical and sub cortical and peripheral

00:36 as well. But they are different that respect. Also as you'll

00:42 acetylcholine acts through both. I wanna nicotine acetylcholine receptors that are receptor channels

00:51 also binds and acts the most formidable G protein coupled receptors as the dominating

00:58 the cardiac muscle. But other I they're transmitters dopamine and histamine or serotonin

01:06 act only through G protein coupled receptor downstream in the cells. Peptides peptides

01:13 be co expressed with amino acid neurotransmitters to non traditional neurotransmitters that we discussed

01:25 lecture where a. T. A denizen gasses, nitrous oxide,

01:42 monoxide under cannabinoids. We also put academic acid here and we said that

02:00 substances are actually very different because those are lipid soluble and that means that

02:07 not stored in the vesicles gasses or the endocannabinoid or economic acid or economic

02:15 precursor for endocannabinoid inside the body that synthesized and a lot of times that

02:22 act in the retrograde fashion. So the pre synaptic terminal is releasing neurotransmitter

02:30 the synaptic terminal has the receptors for neurotransmitter. Then these molecules and the

02:39 and gasses they act onto the pre terminals from post synaptic areas. So

02:46 act in the retrograde like fashion. would be interrogated, synaptic and vice

02:53 . Synaptic pre synaptic would be retrograde this is for gasses and then the

03:04 and we'll talk about in the cannabinoids more. Uh so you had some

03:11 a few slides back question what's the between uh peptides and neurotransmitters? And

03:22 can see that most of the things happened with neurotransmitters, neurotransmitters synthesis americans

03:28 are released neurotransmitter degradation in the synapse re uptake in the synaptic terminal

03:34 transmitter uploading and the vesicles in the synaptic terminal. It's all taking action

03:40 in this area. However, with peptides, it's a little bit of

03:44 story they synthesized on demand and they're from the resources and the selma's of

03:53 neurons and they synthesized on demand only there's really really high levels of

04:00 So a single action potential that travels the external terminal will cause the neurotransmitter

04:06 here of the secular release. But single action potential or just small activation

04:13 are short activation is not going to on the synthesis of their neuro

04:20 This is sustained levels of activity. levels of activity typically can turn on

04:25 production of these neural peptides Again, can be expressed co expressed with

04:31 But they're cycling is different. Once produced, they're loaded into secret

04:38 And unlike vesicles that are only located specialized synaptic locations with small spaces and

04:46 secretary Granules don't always reach the external , and sometimes the content of the

04:54 Granules can be released the longer external here as it is trying to reach

05:01 terminal. So essentially there is no of uh spatial specificity as much of

05:09 special specificity when you're baptized in the Granules as it is for the bicycles

05:15 are located purely in the synopsis. although the secret or grant also being

05:22 toward the synopsis, there might be release of neuro peptides along the way

05:28 have the differences here in synthesis, and storage of these two types of

05:35 . So neurotransmitters, What they're doing uh filling the vesicles and then vesicles

05:44 organelles there of their own plasma membrane these organ al's this plasma member.

05:51 has the views to the plasma membrane the neuron here and in order for

05:59 fusion to take place take place. things need to happen. two Things

06:08 the Menu. Okay? Or means things have to happen. First of

06:17 , you have to have a deep of action production When that deep polarization

06:23 external terminal, it will open bolt calcium channels and so you will have

06:29 densities of voltage gated calcium channels located at the pre synaptic active zones.

06:36 influx of calcium and interaction with calcium a protein complex on the vesicles is

06:43 with this vesicles fuse the membrane and the neurotransmitter release so deep polarization in

06:49 form of the action potential and influx calcium which happens through voltage gated calcium

07:00 . Once calcium enters inside the this is what the outside of the

07:06 is like. It's actually this hairy with all of these different carbohydrates and

07:17 hanging off of it. And when enters some of these proteins on the

07:25 are calcium sensors. One of such synaptic stagnant and enter of calcium and

07:35 of calcium by what is now simplified the snare the secular snare protein complex

07:44 T snare, which is trans membrane complex influx of calcium will allow for

07:51 protein protein complex interaction to take place the protein complexes interact with each

07:57 Then there is the fusion of the membrane within their own own membrane.

08:04 there is excess psychosis of the neurotransmitters exocet. Oh sis this patch of

08:11 number in here. This classical it's going anywhere it buds off and gets

08:18 back into prison at terminal endo psychosis this plasma membrane piece here and then

08:26 of this neurotransmitter bicycle with americans many molecules. These are some of the

08:39 that illustrate some of the features of synopsis and pre sign optically what you're

08:47 at here on the lot this electron image and it shows presumed calcium

08:53 There's little dots here and then. see these craters here. This is

09:00 exercise topic or psychologic fusion pore. essentially looking at the best local coming

09:10 and fusing in the membrane and looking the crater so the neurotransmitter is being

09:16 right now. And this is You see also we talked about the state

09:23 membranes and difficult synapses can be 29 . But then you would have these

09:29 areas where the two membranes come close and form the large gap junction,

09:35 little areas like that. And this where you have gap junctions. Those

09:40 the electrical synopsis, not as dominant the brain as the chemical synopsis,

09:47 very important as we talked about for synchronization of neuronal networks or cells in

09:55 , such as cardiac cells. Now modern day, we are also capable

10:03 not only looking at the anatomy of going on but also looking at the

10:09 of the synopsis and in this diagram probably with the activity. I forgot

10:16 mention to you that at some scientists were very interested about the two

10:24 of the plasma numbering and they were what proteins associated with the cytoplasmic

10:31 brussels cellular side remember it and said would during these experiments very quickly freeze

10:38 patch on the membrane. And they put a little needle or a little

10:47 of glass next to the number and would tap it their junk lit if

10:51 were lucky enough, this frozen piece the number and we'll split up the

10:56 foster lipid bilateral faces would split And so there's a face and there

11:01 a p face. And this was studies to try to address what basically

11:10 elements of the membrane are embedded within or other side or on both sides

11:16 both hostility by labs. And as stimulated and we understood that calcium is

11:24 will also wanted to visualize calcium. so there are guys that allow us

11:30 visualize neuronal activity. And if you're at pre synaptic activity, a good

11:36 to study pre synaptic activity would be in calcium. Because pre synaptic li

11:43 require a lot of calcium influx. synaptic lee will have high densities of

11:50 voltage gated calcium channels allowing for using image calcium concentrations with south africa.

11:59 these images that you're seeing are from dyes that are calcium sensitive dyes are

12:09 that are sensitive to different ions. as the concentration of these ions increases

12:16 dyes will change their reflective or absorptive . And those will be picked up

12:23 the imaging cameras on the microscope. when we talked about, for

12:29 non invasive imaging in the clinics, emission tomography pet scans the first uh

12:36 second lecture of this course. This in the clinics but experimentally we can

12:42 measure ions, we can measure So there are dyes that are sensitive

12:48 voltage. Not just a specific but this is what calcium fluctuations look

12:54 pre synaptic aly. And it shows calcium this is taken from neuron to

13:01 . 4th edition of this bug a of images because they show their clearly

13:08 there are these micro domains of See these little peaks here reading indicates

13:15 concentration of calcium, the highest concentration , a steady state or low levels

13:22 calcium concentration. And when this imaging done it was shown that these migrant

13:32 , these little mountains are corresponding the of these calcium micro domains which would

13:38 to vault educated calcium channels are very associated with these pre active. We

13:46 up exiles where the vesicles are A lot of vesicles are actually primed

13:51 ready to go. A lot of vesicles will be hanging out right by

13:55 membrane, ready to fuse and ready the neurotransmitter release. But so when

14:06 neurotransmitter release happens, this is a without deep polarization and neurotransmitter release.

14:14 this and it shows what happens when is a deep polarization and the pre

14:19 terminal during neurotransmitter release. You can clearly see that first of all,

14:26 a massive increase in calcium concentration threesome lee there's also loss of some of

14:33 spatial specificity and the concentration peaks here calcium. So calcium becomes spatially readily

14:42 throughout the entire pre synaptic area rather being spatially confined to very specific zones

14:51 developers gated calcium channels are located and concentration of calcium can be up to

14:58 micro molar during these kind of uh doing basically deep polarization on particular

15:10 Um For those the gap junctions um for the large in like what like

15:17 causes a larger gap junction and a gap junction. Um Why? Some

15:29 them we don't really know that while have lesser number of gap junctions and

15:37 have more. So there's no no explanation for that. It's not as

15:42 as for example as we know that a lot of voltage gated calcium

15:47 person that there's a lot of voltage sodium channels and potassium channels and runs

15:51 here. But there's not as much understanding and predictability on the spatial

15:58 So the size is uh the gap networks. Now when we talked about

16:07 muscular junction, we said that the potential in the neuro muscular junction,

16:18 neuro muscular junction has include potential and size of that template potential is About

16:30 million malls. So it's massive employee and that's why we said that the

16:35 is always very reliable. There's always to be passed synaptic response, the

16:42 is also very reliable in the sense if there is action potential and motor

16:47 , it will always cause the secular . Now in the central nervous system

16:56 we produce exhibit story post synaptic potentials E. P. S.

17:03 S. Or inhibitory post synaptic potentials . Ps piece. And the single

17:12 can generate an E. P. . B. Or an I.

17:16 . S. B. Of approximately mil of all change. So what

17:24 that tell you? That tells As we spoke from the very

17:28 neurons have to have many excited or activating. Now, neurons also have

17:37 inhibitory synapses projecting onto them and inhibiting activity. So single synapse activation is

17:48 very reliable. What we're talking about If you're at -65 million goals that

17:59 membrane potential And you have the threshold reaction potential of -45 million bowls.

18:12 ? And this is your resting membrane neuronal membrane potential. This is about

18:19 million balls difference. So single synapse to our synapse will cause a deep

18:29 of half mil evolved and it's gonna like this. And if you activate

18:37 may be too excited to the synapses , it will cause a deep realization

18:43 this. You activated 40 or 50 , you may be able to reach

18:51 threshold for actual potential to generate the potential. So you have to have

18:57 of excitatory synopsis in order to cause sufficient deep polarization but not in the

19:04 muscular junction with single synapse causes a of 70 million minutes. And by

19:11 virtue neuro muscular junction synapses are very . That's what I call them.

19:16 fidelity. 121 release of neurotransmitter means twitch of a muscle or contraction of

19:23 muscle, and the central nervous Synopsis are not as reliable because first

19:31 all they produce very small change and need to synchronize and activate 40 50

19:39 100 excited third synapses sometimes in order reach the threshold for the action potential

19:46 . But that is not the case the end plate potential. The other

19:52 is central nervous synapses are capable of release of the neuro cosmetic. That

20:03 that when there is fusion of the to the number rain, not all

20:08 the content gets released, only part the content gets released and that doesn't

20:15 in neuromuscular junctions. So again these nervous system synopses are not as reliable

20:24 two reasons is they're not as strong amplitude and single synapse and be polarizing

20:32 their own. And the second reason sometimes you don't get a full fusion

20:38 pull the secular release but you get a partial fusion. So once the

20:44 are loaded they're docked in these areas actor zones you need energy. So

20:52 production of a teepee and other factors facilitate the priming of these vesicles very

20:58 to the areas where you have both calcium generals. And then there's deep

21:05 voltage gated calcium channels will allow influx calcium and binding of calcium to the

21:13 Curtin complex will allow for the membrane fuse. And in some instances there

21:21 not be enough calcium for one reason another, maybe there wasn't enough calcium

21:26 the extra cellular calcium environment. Maybe educated calcium channel was not opening properly

21:35 you get partial fusion for opening and it actually goes back into this position

21:45 back into this position to be dark prime again. So it's called the

21:49 and run. So this is not full commitment here. You don't release

21:55 of the neurotransmitter. You just kiss the membrane and release a little bit

22:00 run in most cases though. And there is sufficient enough calcium levels there

22:06 be full fusion. And that means the poor the fusion poor will open

22:12 and dilate and will cause the full of the chemical into the synopsis following

22:22 you have to recycle this piece of number. And so this piece in

22:26 membrane gets tagged. There are usually and tags for pieces of the membrane

22:32 basically you are a vesicles that have released the neurotransmitter. We're gonna coach

22:39 with molecules such as Claritin for And then it gets recognized as an

22:45 bicycle that's coated with Claritin and it have two pathways that can go back

22:51 the early end of cell and get and this bigger cattle here and made

22:58 a new bicycle. Or it can filled with protons. In both cases

23:07 gets acidified with high proton gradient inside vesicles. And that high proton gradient

23:15 mechanisms will encourage to upload neurotransmitter neurotransmitter is going to be specific transporters,

23:24 transporters on these membranes that will be with the help of this high protium

23:32 h plus gradients and then re filled are going to be positioned again in

23:38 dark prime positions for the subsequent So this whole process from the release

23:47 the neurotransmitter gets released and the synapse active and is releasing neurotransmitters And for

23:55 synapse to fully reload All of the . I'm not talking about one,

24:00 let's say the synapse had thousands of ready. You got big stimulus,

24:07 got released vesicles non stop for a seconds. It's gonna take about 12

24:14 for the system to recovering. So finite. There is a certain

24:22 Uh These neurotransmitters. The interesting thing for employee potential. Each vesicles will

24:30 a quanta Of about 2000 to What kind of chemical and neuro muscular

24:42 . Acetylcholine. So a single vertical neuro muscular junction will contain a quanta

24:50 these molecules. 2000 to 4000. see what kind of point it is

24:55 one or 2, 2002 or but it's not 20 and 2000.

25:01 there is basically the reason why the potential will be approximately 70 million

25:09 Because some, some vesicles will contain . Some vesicles will contain 3,421

25:19 Others will contain 2850 or whatever number exact molecules that get loaded up into

25:27 vessel. So you can also estimate many acetylcholine receptors you can activate because

25:36 I if you recall, I told that it takes to acetylcholine receptor molecules

25:41 open nicotine acetylcholine receptor channel. So have 2000. That means you can

25:48 1000 channels. And if you think , oh well wait a second,

25:53 I can go back. What I in the first course about conductance is

25:57 conductance. As individual conductance is of channels. And now I can figure

26:03 that if it's 70 million balls and because of the 4000 molecules, it

26:07 it's 2000 channels that are open. much of the middle levels each channel

26:15 , how much of the current each contributes or conductance is. You can

26:18 calculate it and derive it for total . And also individual channel conductance

26:24 The other thing I want to address is look what happens when there's a

26:30 of this bicycle to the plasma What happens to the surface area of

26:37 terminal? It increases and this is , but what if you're binding 100

26:45 bicycles, you actually significantly increase the area, which increases which property of

26:54 plasma membrane, the capacitance property of plasma membrane, larger surface area and

27:00 surface area. The more charge can stored so momentarily or during the the

27:07 release, the capacitance of the cell up. You can actually measure increases

27:14 capacities of the cell membrane during this release. Now, once it gets

27:22 coast again, the capacities goes back the pre uh vesicular release levels to

27:30 same surface area levels, steady More or less, it's always

27:34 Yeah. So given that that process , what happens if there's any

27:45 any any any point issues with which I mean you have all sorts of

28:03 have all sorts of problems. If can't release vesicles, that means the

28:07 of communicate properly. You cannot recycle . That means the kind of community

28:16 properly if you cannot synthesize. Because I mentioned that those mean systems,

28:23 are responsible for different behaviors, but also are correlated with distinct neurological

28:30 Dopamine neurological disorders are typically motor disorders Parkinson disease, serotonin and improper serotonin

28:43 is typically with psychiatric and mental depression, anxiety, uh eating

28:54 So and it depends then. So if you lose one of these

29:00 in the brain that synthesizes acetylcholine, deprive the whole brain potentially of this

29:07 molecule which plays a very important But it just depends where that

29:13 Uh and it's very common that neurological have to do with post synaptic receptor

29:23 . At least we understand that better the pre synaptic but they're definitely effects

29:28 the pre synaptic side. Especially an to release inhibitory neurotransmitters or enough of

29:34 inhibitor. And our transmitter. Question when does when does the when

29:44 they open up when the action potential ? Okay, so that's that's the

29:52 the voltage opens these channels? You to have a it can be it

30:10 be a lot of times adjustable fusion it can have partial fusion and that's

30:16 that's different from neuro muscular junction, calcium levels and interaction of this podium

30:25 complex that has to uh use. it's a pretty reliable system. It's

30:32 as reliable. I'm not saying it's all the time, you know,

30:35 then every time you would try to know, produce a something complex,

30:41 emotionally, you know, motor you would be failing at it,

30:45 know trying to press a keyboard and can't do it. So so it's

30:49 that it happens often. It's just we have to engage multiple sin

30:55 We have to release multiple vesicles in to reach the threshold and a lot

31:01 them will be fully fused and release full content. But some of them

31:05 have this partial fusion and that's what a central nervous system more complex and

31:10 understanding and not as reliable as neuromuscular it is not to say that it

31:16 not reliable. Mhm. Okay, questions. Now, let's see.

31:28 talk about E. P. P. Since I started talking about

31:31 . P. S. P. . We're gonna come back to the

31:33 diagram. So E. P. . P. S. Again the

31:37 E. S. Synaptic people So when you have the release of

31:47 and glutamate will bind to glutamate for channels that will cause influx of sodium

31:52 other things that will cause this deep . We'll also see that the also

32:00 deepness of compassion and we'll study that . But this is excitatory post synaptic

32:05 . Those are going to be a synapse. E. P.

32:10 P. S. Only on the about half a mil level and change

32:15 the number of potential post synaptic This is pre synaptic PPS PPS.

32:24 synaptic recording a level of depersonalization. synaptic these are graded potentials. So

32:32 can be half a little ball Two balls. Formula balls. They're graded

32:38 size action potentials is all or meaning that once it reaches the threshold

32:45 action potential opens up both of created channels more so more. There's you

32:50 stop an action potential after mindless 45 . If it reaches that level,

32:56 cannot stop the action potential. But E. P. S.

32:59 S. If it goes to minus minus 16 minus it can come back

33:05 the same for I. P. . P. S. So they're

33:09 , they're not all or none like action potentials. I PS PS is

33:17 binding of Gaba to Gaba receptor channels then one there are two subtypes.

33:23 Gaba receptor channel A gaba a will for influx of chloride influx of so

33:33 a positive charge causes deep polarization, of chloride negative charge causes hyper polarization

33:42 the form of inhibitory cost synoptic I PSP. So as the cell

33:51 trying to reach the threshold for action , this cell is not only receiving

33:57 inputs, it's also receiving inhibitory And only that reaches the threshold will

34:06 the action potential. Mm. So cells neurons will have pre synaptic excited

34:16 synaptic inhibitory inputs coming in suddenly have of thousands of them in one

34:24 It can happen at the same time they happen at the same time they

34:28 in time if it happens in the area, the summit in space and

34:34 more they some aids in deep The better chance they have to reach

34:41 threshold to generate the action potential. , these are synaptic potentials. All

34:52 potentials are graded, excited during inhibitory potential is all or none.

35:00 So when we talk about ion a signaling its ligand gated channels, ligand

35:09 to these receptors proteins and these receptor are also channels that allow for the

35:16 of ions in this case chloride. it's ion a tropic versus metabolic

35:24 It's G protein coupled with suffers a , binds to the receptor and causes

35:35 effect on the G protein. It's with this G protein complex activating this

35:43 complex can gain ion channel. So there's no flux through this receptors that

35:52 played in a couple of receptor, no ion flux but it can nearby

35:57 the channels and open nearby channels and talk about that and in the next

36:03 of lectures it can also activate it can activate secondary messengers through this

36:13 tropic signaling. It can activate transcription at the level of the soma and

36:20 nucleus of the cell. So medical signaling is only indirectly. That's what

36:30 , indirectly can affect bionic channels, of ions and can exert intracellular effects

36:41 the cellular cascades and cellular messengers inside cells. Same neurotransmitter, different

36:52 Same. Your consumers are different effects different selves. We'll look at this

36:55 a little bit but this is one our favorite molecules that we are

37:02 seed alkaline and so you understand a about acetylcholine and I'll ask you a

37:08 of questions about acetylcholine, acetylcholine is natural agonist for ion a tropic

37:15 Acetylcholine receptor channels and formidable tropic masculinity in coupled receptors you don't make

37:28 Acetylcholine is a natural agonist. When receptors nicotine is an agonist for the

37:36 casino calling the sentence must korean. substance in nature is a natural agonist

37:44 . What is an agonist agonist is that opens the channel or encourage the

37:50 channel activity in the case of indirect antagonist is something that blocks and closes

37:57 channel. So we already know about antagonist. We know about the voltage

38:03 sodium channel antagonist called tetrodotoxin that was in in puffer fish and newts and

38:13 . So your area is actually another poison from little tropical frogs and curare

38:24 an antagonist to nicotine suckers. And is another chemical that is an antagonist

38:32 most clinical research. So they're not distinguished based on uh on their own

38:41 tropic versus metal tropic, they have distinct neuro pharmacology. So now you're

38:48 neuro pharmacologists, that's when you're starting understand what substances bind to what

38:54 what effect it has on our channels downstream on the south the mechanisms of

39:00 of different drugs, endogenous molecules and uh pharmaceutical pharmacological agents. So these

39:11 the major receptors. Now acetylcholine has be synthesized and acetylcholine gets synthesized when

39:21 molecule and the way come together and , this is calling the citadel

39:31 But if you remember get together and and you know that this is a

39:37 everyone. And this is coding molecule synthesized, it's transported here loaded up

39:48 new bicycle. And then when there a proper signal signal coding molecules can

39:53 released here into the synaptic. Once released into the synaptic flat they will

40:02 a clinic and acetylcholine receptors in the . So you have both types on

40:07 tropical metal tropic a ch receptors in cns but also there will be

40:15 So there is a degradation enzyme as call it nestor race that breaks down

40:23 societal covina Siegel cohen asteroids breaks it into Colin and acetic acid call IAN

40:32 transported back pre synaptic aly into the where it comes together with a single

40:40 and chats to make cola molecules and the cycle. So motor neurons will

40:55 a little cold in but in neuro junction you only have nicotine in a

40:59 code in the suffers all quick angry and parasympathetic nerve endings will have acetylcholine

41:08 the brain. We have acetylcholine in specific nucleus and that acetylcholine specific nucleus

41:15 target academic and masculine acetylcholine. So talked about Alzheimer's disease in the first

41:24 of the course when we looked at hallmarks pathological hallmarks of Alzheimer's disease And

41:29 remind you we talked about intracellular Nurofen, broccoli tangles and we talked

41:36 extra cellular plaques. Beta amyloid plaques some of the cellular features hallmarks of

41:45 pathology. We also talked about how are gross anatomical changes and significant loss

41:53 nervous tissue, especially gray matter in C. N. S. In

41:58 advanced stages of Alzheimer's disease and we about a little bit of the

42:04 how Alzheimer's disease is prevalent. Is prevalent in the older population.

42:13 talked about symptomology of memory loss but other significant things that happen with the

42:23 and progression of the severity of this leading to eventually to death. Now

42:29 turns out that acetylcholine and the seed cells are very susceptible and get damaged

42:42 on in the Alzheimer's disease. So is an important molecule for cognitive function

42:51 for memory formations and most of the in the market for Alzheimer's disease.

42:59 hot now with come symptomology mechanisms therapy we're talking about neural pharmacology. So

43:09 start talking about therapy treatment of diseases this case Alzheimer's disease. The most

43:16 drugs on the market are a single to race inhibitors. So think about

43:23 . If you take out a seal Esther race, what do you do

43:28 settle coleene? Do you make more call in? Do you affect the

43:37 of the you cut down on the on the breakdown of the pseudo

43:49 Right. And when you reduce the when you block the subtle cola

43:56 What you do is you increase the or you can call it bio

44:03 how much of that molecule is You increase the availability of that a

44:09 colony number synapse. You give this a chance to linger longer in the

44:16 here. So you don't have enough acetylcholine and most of it will bind

44:22 the receptors to have an effect rather being degraded and recycled. Yeah.

44:30 what happens? It's like uh yeah that that can happen but typically not

44:43 Alzheimer's medications and the doses that are used that's not a very common thing

44:50 restoration universe. Um Most of the problems with overdosing is with opioids with

44:58 medications. Uh Here there's another issue . And let me tell you

45:06 you're losing acetylcholine synthesis and you lost neurons. Do you think this medication

45:14 going to be effective? If there's more subtle choline you're gonna put inhibitor

45:27 it's inhibiting inhibitor but there's no So again, most of the mechanisms

45:38 action of the Alzheimer's medications drivers will as the top kill unnecessary inhibitor

45:44 Since Call Industries inhibitors, you'll even commercials on T. V.

45:48 C. I. N. Sin. Are you any sin medications

45:52 for some older individual medications and things that? How long did the Civic

46:00 last if you're using? Oh that depends on the dose is it depends

46:05 the state of the disease, depends the brand of the medication your neurologist

46:12 to you. But it's a They're quite an effective. It's a

46:21 huge, huge multibillion dollar industry that drugs can slow down the progression of

46:27 disease. there's no cure. So not therapy to cure Alzheimer's disease,

46:33 no cure for Alzheimer's disease. We slow down the progression of this

46:39 but we need other alternatives, we other things. And so I always

46:47 to my students in this course, guys have to figure out other

46:52 just eat acetylcholine and just eat You know, why can't you just

46:58 it if your brain doesn't make You know, we first tried to

47:02 laugh at it and you're like, well maybe there's something to do with

47:07 precursors. You know, if I synthesize this molecule, maybe maybe I

47:14 somehow artificially stimulate the precursors and and maybe there's a little bit of a

47:21 golden chat left in there. So start strategizing and thinking different things,

47:28 know? What about receptors? The is not that I didn't say the

47:33 is not that eventually there isn't going be a receptor because if the receptors

47:39 serving a function that has no chemical it is being bound to a lot

47:45 receptors can buy many chemicals so they still be there. So I didn't

47:49 the receptors are all gone. So can't we have a substance that mimics

47:57 in the brain, how are you take that in your mouth, then

48:03 on your gut, it's gonna affect of this little building receptors all over

48:08 body, all over your muscles, that effective? So you have to

48:14 the blood brain barrier right? Whatever put in your mouth has to cross

48:19 blood brain barrier. Nasal sprays. talking about COVID-19 infections through the openings

48:28 the skull. Yeah very effective way delivering drugs. Yeah nasal spray of

48:38 Siegel calling safe like analog in the lobe that that that that binds up

48:45 the receptors so the future is yours all of these ideas and much better

48:53 you guys can put to practice and new drugs because we need we need

48:59 a it's a terrible disease because the is alive but they're not there you

49:04 . So every disease is really terrible it's a huge burden on others.

49:13 let's talk a little bit more about pharmacology uh poisoning neurotransmitter release. It's

49:20 be a book of special interests spiders, snakes and you. I

49:28 just listening to a program on NPR lady said she was hiking and fell

49:35 by the pond someplace in the mountains woke up like surrounded by frogs like

49:40 of frogs came out of the pond the person that was interviewing. Well

49:45 not so bad. It could have snakes. Talk about spider snakes and

49:52 because a lot of these little creatures very potent toxic molecules toxic to

50:05 So ah black widow spiders can be bite of the spider can be

50:18 And a lot of these natural substances interact with the neurotransmitter release. Uh

50:27 studio butcher Lionel for example, anybody about botulism, heard about botulism.

50:35 uh it's a disease that is not prevalent and and developed advanced countries.

50:41 if you have bad canned food that gone bad, there are Australian botulinum

50:53 to try and start producing a bunch lines on toxins and you can get

50:59 can get food poisoning. You can be deadly in some cases and you're

51:06 invited to a Botox party. So not eating bad canned food, you

51:14 get much a line of toxins in controlled medical spa, beauty fashion or

51:22 an FDA approved pharmacological treatment. So turns out that Botox is an abbreviation

51:35 much a lot of the toxin. not stated on the beauty magazines that

51:41 a toxin that is being injected Botox spun, right, you get service

51:47 of champagne, relax in the chair a friday and get some injections down

51:52 your areas of interest on the face . And what it does is a

52:00 of uh people would leave Botox parties they would also put fillers on their

52:09 . So that looks really big. in addition to being blue it may

52:15 be able to move, it looks well and speak very well, pronouncing

52:21 and that's because what Botox does It interacts with the Seattle Colin bicycle

52:31 and the seed locally in release onto muscles. So why would you do

52:37 ? And why do people do it beauty reasons as we age? And

52:42 muscles move and remove the skin and skin changes because of the sun and

52:50 and things like that. And you wrinkles. A lot of people don't

52:56 wrinkles and when you block the secular and the stimulation of the muscles,

53:02 actually relaxes some of the wrinkles. people look more beautiful, more attractive

53:12 is a different thing phillips. You're injecting, filling the space with something

53:16 fluid that stays there for a The Botox. You're blocking neurotransmitter release

53:22 one of the consequences would be that cannot move your muscles as well as

53:28 speaking following the injections. So when go and get a dental work done

53:36 you have a local anesthesia. Sometimes also will have difficulty chewing right

53:41 But this is a little different. this is now you block the neural

53:48 and you relax the muscles essentially from and therefore you relax the wrinkles.

53:57 beauty focuses. Now there's also another of Botox and that's an FDA approved

54:08 injections to treat migrates. Um so a wide commute of all of the

54:21 of applications that you can come up one molecule first to discover it and

54:29 bad canned food and you get poisoned then you discover the mechanism of action

54:37 that budget line on toxin that it with acetylcholine release. Then you discover

54:45 it specifically interacts with the protein protein in the physical er release. Then

54:52 start using it for beauty purposes and you discover that it may have an

54:58 which people are using it for beauty . A lot of people have come

55:02 to get Botox or so it would my migraine. There's people that do

55:07 , they still have migraines and other . So there was a little bit

55:10 a notice there and then there were that came out and sure enough it's

55:14 approved medication approved treatment. And so many different substances in nature that will

55:23 with pre synaptic also with post synaptic receptors. It can target the release

55:33 Macedo calling. It can target the synaptic receptors and block post synaptic academic

55:42 masculine and acetylcholine receptors. And in to these medical things, humans also

55:53 molecules and these molecules and apostates are acting the same way. Organophosphates are

56:05 seed Alcala nestor race inhibitors. So phosphates are used in some agricultural applications

56:18 organophosphates and humans always when they make things there's bad guys that make bad

56:26 or good guys that make bad things accident and bad guys continue using those

56:31 things. So organophosphates are nerve siren. So mon and nerve gasses

56:43 being used by shady governments and terrorist around the world, There was a

56:49 incident in Tokyo Metro in the 90s Nerve gas was released and killed poisoned

56:57 . I believe there were nerve gasses were being used in the lost conflict

57:04 takeover of syria as well. So there's still stockpiles of these biological and

57:14 weapons. Now, what is so ? And maybe that was the

57:22 How do you overdose from that What is so dangerous and why would

57:26 nerve gas kill you? Because that's whole unnecessary inhibitors should help you with

57:30 Alzheimer's disease. However, those receptors involved in the continuing receptors are involved

57:38 the contraction of the diaphragm to breathe exposure to nerve gasses. Nerve gasses

57:45 used in, when the United States into Afghanistan went on into Iraq.

57:52 were used in Fallujah, one of big areas that were used to.

57:56 how do they kill you? They block the breathing and shut down the

58:03 . So it's not necessarily that they you because they block your receptors in

58:09 brain, but it can also start seizures and uh again, these are

58:19 interesting parallels where you have nature that hurt you, you can take advantage

58:27 that nature and turn it into a treatment you can turn it into from

58:32 collage vehicle drug, you can also it into a weapon and when you

58:37 it into a weapon, these mechanisms action that you have in the brain

58:44 , acetylcholine and the receptors person actually you have it will also be inside

58:49 the body. Therefore the effect of lot of the substances, especially volatile

58:54 such as gasses will be a systemic not just on the brain but on

58:59 whole on the whole body the whole system. So let me see what's

59:09 next area that we're about to get . A subtle Colin uh agonists,

59:17 . And we're gonna review other category serotonin and the cannabinoids, glutamate,

59:26 neurotransmitters, labeling and some other good . So we're gonna leave this information

59:31 next week. I think it's sufficient information for this week for everybody uh

59:38 so have a good weekend and I'll you next week. Yeah. Sorry

59:47 didn't get the last

-
+