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Module 202: Fundamental neuroscience and the brain > Theme 1: Lecture 4 - Chemicals in the brain > Flashcards

Theme 1: Lecture 4 - Chemicals in the brain Flashcards

(54 cards)

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1
Q

What are the categories of neurotransmitters

A

Amino acids
Monoamines
Acetylcholine
Neuropeptides

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2
Q

Which are the small, fast categories of neurotransmitters

A

Amino acids
Monoamines
Acetylcholine

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3
Q

What is the large, slow category of neurotransmitters

A

Neuropeptides

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4
Q

Describe small, fast neurotransmitters

A
  • Synthesized locally in the presynaptic terminal
  • Stored in synaptic vesicles
  • Released in response to local increase of Ca2+
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5
Q

Describe large, slow neurotransmitters

A
  • Synthesized in the cell soma and transported to the terminal
  • Stored in secretory granules
  • Released in response to global increase in Ca2+
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6
Q

Which neurotransmitters are released in response to low frequency stimulation

A

Fast neurotransmitters

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7
Q

Which neurotransmitters are released in response to high frequency stimulation

A

Slow and fast neurotransmitters

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8
Q

What is the excitatory amino acid neurotransmitter in the CNS

A

Glutamate (Glu)

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9
Q

What are the inhibitory amino acid neurotransmitters in the CNS and where do they act

A

GABA (y-aminobutyric acid) in the brain

Glycine (Gly) in the spinal cord and brain stem

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10
Q

How is glutamate synthesized

A

It is synthesized in the presynaptic terminal from 2 sources:

  • From glucose via the Krebs cycle
  • From glutamine converted by glutaminase into glutamate
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11
Q

How is glutamate loaded and stored in vesicles

A

By vesicular glutamate transporters (VGLUTs)

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12
Q

How is Glutamate taken back up after release

A

By excitatory amino acid transporters (EAATs) in the plasma membrane of the presynaptic cell and surrounding glia

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13
Q

What happens to glutamate when it has been taken back up after release

A

Glial cells convert the glutamate to glutamine which is transported from the glia back to the nerve terminals where it is converted back into glutamate

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14
Q

How is GABA synthesized

A

It is synthesized from glutamate in a reaction catalysed glutamic acid decarboxylase (GAD)

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15
Q

How is GABA loaded and stored in vesicles

A

By a vesicular GABA transporter, GAT (glycine uses the same one)

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16
Q

How is GABA taken back up after release

A

Using transporters on glia and neurons including non-GABAergic neurons

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17
Q

What happens in cerebral ischaemia

A
  • The metabolic events that retain the electrochemical gradient are abolished
  • Reversal of the Na+ / K+ gradient
  • Transporters release glutamate from cells by reverse operation
  • Excitotoxic cell death (Ca2+ -> enzymes -> digestion)
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18
Q

What does GHB y-hydroxybutyrate (date rape drug) do

A
  • A GABA metabolite that can be converted back to GABA
  • Increases amount of available GABA
  • Too much leads to unconsciousness and coma
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19
Q

What are the 2 groups of molecules that make up monoamine neurotransmitters

A

Catecholamines and Indolamines

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20
Q

What neurotransmitters are catecholamines

A

Dopamine
Epinephrine
Norepinephrine

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21
Q

Which neurotransmitter is an indolamine

A

Serotonin (5-Hydroxytryptamine, 5-HT)

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22
Q

How is dopamine synthesized

Study These Flashcards
A
  • Tyrosine is converted to L-Dihydroxy-phenylalanine (dopa) by the enzyme tyrosine hydroxylase which adds an alcohol group
  • Dopa is converted into dopamine by the enzyme dopa decarboxylase which removes a carboxylic acid group
23
Q

Why is Levodopa (dopa) significant

Study These Flashcards
A

it can be used to treat Parkinson’s disease

24
Q

How is norepinephrine synthesized

Study These Flashcards
A
  • Dopamine is converted to norepinephrine by the enzyme dopamine B-hydroxylase (DBH) which adds an alcohol group
  • DBH is located only in synaptic vesicles so norepinephrine is the only neurotransmitter synthesized within vesicles
25
How is epinephrine synthesized
Norepinephrine is converted into epinephrine by the enzyme phentolamine N-methlytranferase (PNMT) which adds a methyl group
26
How are catecholamines loaded and stored in vesicles
By vesicular monoamine transporters (VMATs)
27
How are catecholamines released
By Ca2+ dependent exocytosis
28
How are catecholamines taken back up after release
By transporters powered by electrochemical gradient: - Dopamine transporters (DATs) - Norepinephrine transporters (NETs) ect
29
What happens to catecholamines once they have been taken back up into the cell cytoplasm
-Reloaded into vesicles -Enzymatically degraded by Monoamine oxidases (MAOs) OR -Inactivated by Catechol-O-methyl-transferase (COMT)
30
What does amphetamine do
Reverses catecholamine transporter, so pumps out transmitter and blocks reuptake (DA & NE)
31
What does cocaine and methylphenidate (Ritalin) do
Block DA reuptake into terminals. More DA in synaptic cleft – extended action on postsynaptic neuron.
32
What does the drug Selegiline do
Monoamine oxidase (MAO) inhibitor found in dopaminergic nerve terminals. Prevents the break down of DA, allowing more to be released on subsequent activations and overall increasing the available amount of DA.
33
What is selegiline a treatment for
early-stage Parkinson's disease, depression and dementia
34
What does entacapone do
Catechol-O-methyl-transferase (COMT) inhibitor, increases the available amounts of catecholamine neurotransmitter
35
What is entacapone a treatment for
Parkinson's disease
36
How is serotonin synthesized
- Tryptophan is converted into 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase which adds an alcohol group - 5-hydroxytryptophan is converted into 5-hydroxytryptamine (serotonin) by the enzyme 5-HTP decarboxylase which removes a carboxylic acid group
37
How is serotonin taken back up after release
By serotonin transporters (SERTs) on the presynaptic membrane
38
What happens to serotonin after it is taken back up into the cytoplasm
It is destroyed by monoamine oxidases (MAOs)
39
Name the drugs which affect catecholamine release and reuptake
``` Amphetamine Cocaine Methylphenidate Selegiline Entacapone ```
40
Name the drugs which affect serotonin release and reuptake
Fluoxetine Fenfluramine MDMA (ecstasy)
41
What does the drug Fluoxetine (Prozac) do
blocks reuptake of serotonin (SSRI – selective serotonin reuptake inhibitor)
42
What is the drug Fluoxetine (Prozac) a treatment for
Depression | OCD
43
What does the drug Fenfluramine do
- Stimulates the release of serotonin and inhibits its reuptake - (has been used as an appetite suppressant in the treatment of obesity)
44
What does MDMA do
Causes NE and serotonin transporters to run backwards, releasing neurotransmitter into synapse/extracellular space (assessed for therapeutic potential in PTSD)
45
How is acetylcholine formed
``` Choline acetyltransferase (ChAT, CAT) converts choline + Acetyl CoA (coenzyme A) into acetylcholine. ```
46
How is acetylcholine packaged into vesicles
By vesicular acetylcholine transporter (VAChT)
47
What happens to acetylcholine after it has been released into the synaptic cleft
- It is rapidly degraded by acetylcholinesterase (AChE) | - Choline is transported back into the presynaptic terminal and converted into acetylcholine
48
Give an example of a an acetylcholinesterase inhibitor
Neostigmine
49
What is the chemical structure of neuropeptides
Short polypeptide chains 3-36 amino acids long
50
Name 5 types of neuropeptides
``` Endorphins Neuropeptide Y Substance P Endogenous opioids Vasopressin ```
51
Describe neuropeptide release and degredation
- Follow the secretory pathway and NOT released in the same manner as small molecule transmitters - Dense core vesicle fusion and exocytosis occurs as a result of global elevations of Ca2+ (sustained or repeated depolarization or release of Ca2+ from intracellular stores) - Neuropeptide vesicle membrane recycled but not refilled - Bind to and activate receptor - Neuropeptides signalling is terminated by diffusion from site of release and degradation by proteases in the extracellular environment - Release is slower than small molecule release and signals may be maintained for longer
52
What are endocannabinoids
Small lipids which mostly cause reduced GABA release at certain inhibitory terminals
53
Describe how Nitric Oxide works as a retrograde signaller
- The gas is not stored but rapidly diffuses from its site of synthesis. Diffuses between cells (into presynaptic cell -> retrograde transmitter) - Activates guanylyl cyclase which makes the second messenger cGMP - Within a few seconds of being produced NO is converted to biologically inactive compound (switching off the signal) - Potentially useful for coordinating activities of multiple cells in a small region (tens of micrometers) (how big is a neuron?)
54
How is Nitric Oxide made (in the context of a neurotransmitter)
It is made in the postsynaptic neuron by nitric oxide synthase which is activated by the binding of Ca2+ and calmodulin

Module 202: Fundamental neuroscience and the brain (2 decks)

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