L4 Chemicals in the Brain

Question 1

How are amino acid, monoamine and acetylcholine neurotransmitters synthesised?

Answer 1

Locally in the presynaptic terminal.

Question 2

How are amino acid, monoamine and acetylcholine neurotransmitters stored?

Answer 2

In synaptic vesicles.

Question 3

How are amino acid, monoamine and acetylcholine neurotransmitters released?

Answer 3

In response to local increases in Ca2+.

Question 4

How are neuropeptides synthesised, released and stored?

Answer 4

Synthesised in the cell soma and transported to the terminal.

Question 5

How are neuropeptides released?

Answer 5

Released in response to global increases in Ca2+.

Question 6

How are neuropeptides stored?

Answer 6

Stored in secretory granules (dense core vesicles).

Question 7

Which neurotransmitters are fast?

Answer 7

Amino acids as they are docked in vesicles near the membrane.

Question 8

Which neurotransmitters are slow?

Answer 8

Neuropeptides are they are larger and stored further away.

Question 9

What frequency stimulations are required to release fast and slow neurotransmitters?

Answer 9

Fast NT- Low frequency

Slow NT- High frequency

Question 10

Why do slow neurotransmitters require high frequency stimulation?

Answer 10

There needs to be a larger diffuse increase in Ca2+. High frequency is rapid and sustained.

Question 11

What are the main excitatory neurotransmitters?

Answer 11

Depolarises.
Fast transmission.
Glutamate (AA, CNS).

Question 12

What are the main inhibitory neurotransmitters?

Answer 12

Hyperpolarises.
Fast transmitters.
GABA (AA, brain).
Glycine (SC and BS, AA).

Question 13

What is an example of a diffuse modulatory system?

Answer 13

Serotonergic system, a small set of neurones, that mostly arise from the brainstem, whose axons innervate far away.
(Also dopamine or acetylcholine)

Question 14

What is the function of the serotonergic system?

Answer 14

Mood, sleep, pain, emotion, appetite.

Question 15

What is a diffuse modulatory system?

Answer 15

Neurotransmitters that modulate rather than transmit information.

Question 16

Where and how is glutamate synthesised?

Answer 16

Presynaptic terminal from Krebs glucose or glutamine (converted by glutaminase).

Question 17

How is glutamate stored?

Answer 17

Loaded and stored in vesicles by vesicular glutamate transporters (VGLUTs).

Question 18

How is glutamate reuptaken?

Answer 18

Excitatory amino acid transporters (EAATs_ in the plasma membrane and glia.

Question 19

What go glia do to glutamate?

Answer 19

Convert glutamate to glutamine and transport it back to the nerve terminals where it it converted back to glutamate.

Question 20

How many layers does the cortex have?

Answer 20

Six.

Question 21

How is GABA synthesised?

Answer 21

From glutamate, catalysed by glutamic acid decarboxylase (GAD).
A higher proportion is made de novo than through recycling.
Main inhibitory enzymes can be synthesised from the excitatory.

Question 22

How is GABA stored?

Answer 22

Loaded and stored in vesicles by a vesicular GABA transporter (GAT).

Question 23

How is GABA cleared from the synapse?

Answer 23

Reuptake by glia and neurone transporters (co-transport with Na+), including those on non GABAnergic neurones.

Question 24

What happens if you have too much glutamate or too little GABA?

Answer 24

Hyperexcitability leading to epilepsy and excitotoxicity.

Question 25

What happens if you have too much GABA?

Answer 25

Sedation/coma.

Question 26

What does cerebral ischaemia cause?

Answer 26

The metabolism that maintain the electrochemical gradient is abolished, Na/K gradient is reversed. Transporters release glutamate leading to excitotoxic cell death.

Question 27

How does excitotoxicity cause cell death?

Answer 27

Too much calcium from the excitement which activated enzymes that digest cells irreversibly.

Question 28

Which neurotransmitters are local?

Answer 28

GABA, glycine and glutamate.

Question 29

What is GHB?

Answer 29

Date rape drug. | GABA metabolite that can be converted to GABA, increases the amount causing unconsciousness/coma.

Question 30

Which monoamine neurotransmitters are catecholamines?

Answer 30

Dopamine Noradrenaline Adrenaline (hormone)

Question 31

Which monoamine neurotransmitters are indolamines?

Answer 31

Serotonin

Question 32

How is dopamine synthesised?

Answer 32

Two stages. | From tyrosine to dopa and then dopamine.

Question 33

What drug can be administered to increase dopamine levels and for which disease?

Answer 33

Levodopa (dopa) for treat Parkinson's. | Converted to dopamine by dopa decarboxylase.

Question 34

How are noradrenaline and adrenaline synthesised?

Answer 34

Only in the vesicles. | From dopamine to noradrenaline and then adrenaline.

Question 35

How are the catecholamines stored?

Answer 35

Vesicular monoamine transporters (VMATs) load into vesicles via a proton gradient.

Question 36

How are catecholamines released?

Answer 36

By Ca2+ dependant exocytosis.

Question 37

How are catecholamines reuptaken?

Answer 37

Dopamine transporters (DATs) and noradrenaline transports (NETs) using an electrochemical gradient.

Question 38

What happens after the reuptake of catecholamines?

Answer 38

Reloaded into vesicles or enzymatically degraded by monoamine oxidases (MAOs) or inactivated by catechol-o-methyl-transferases (COMT).

Question 39

How does amphetamine (adderall) modulate the catecholamines?

Answer 39

Reverses the transporter causing the NT to be pumped out and blocks reuptake. This lengthens the action.

Question 40

How does cocaine and methylphenidate (Ritalin) modulate dopamine?

Answer 40

Blocks reuptake, extending action.

Question 41

How does selegiline modulate dopamine?

Answer 41

MAO inhibitor, prevents breakdown so more is released in subsequent activations. Use to treat early PD, depression and dementia.

Question 42

How does entacapone modulate dopamine?

Answer 42

COMT inhibitor, increases amount of available NT. | PD treatment.

Question 43

How is serotonin synthesised?

Answer 43

2 stages. | Tryptophan to 5-HD then serotonin.

Question 44

How is serotonin stored?

Answer 44

Stored in vesicles.

Question 45

How is serotonin reuptaken?

Answer 45

``` Serotonin transporters (SERTs). Destroyed by MAOs in the cytoplasm. ```

Question 46

How does fluoxetine (Prozac) modulate serotonin?

Answer 46

Selective serotonin reuptake inhibitor (SSRI) | Treatment of depression and OCD.

Question 47

How does fenfluramine modulate serotonin?

Answer 47

Stimulates release and blocks reuptake (appetite suppressant in obesity).

Question 48

How does MDMA (ecstasy) modulate serotonin?

Answer 48

Amphetamine Causes noradrenaline and serotonin transporters to run backwards, releasing NT into the synapse. Therapeutic potential for PTSD.

Question 49

How is acetylcholine synthesised?

Answer 49

Choline acetyltransferase converts choline and acetyl coA into acetylcholine which is packaged into vesicles by vesicular acetylecholine transporter (VAChT).

Question 50

How is acetylcholine degraded?

Answer 50

In the synaptic cleft by acetylcholinesterase (AChE) and choline is transported back to form acetylcholine.

Question 51

What are acetylcholinesterase inhibitors?

Answer 51

Block breakdown of ACh, prolonging its action in the cleft. | Neostigmine, used for myasthenia gravis (MG).

Question 52

What are neuropeptides?

Answer 52

Slow transmission Short peptide chains of 3-36 AAs. Endorphins, substance P. neuropeptide Y, endogenous opioids and vasopressin (ADH).

Question 53

How are neuropeptides synthesised?

Answer 53

Much faster than small molecule transmitters. Secretory pathway. Synthesised in the neurone nucleus, precursors and enzymes are transported down the axon to the terminal where the NP is produced.

Question 54

How are neuropeptides degraded?

Answer 54

Proteases in the extracellular environment.

Question 55

How can Nitric oxide by used in retrograde signalling?

Answer 55

NO is made in the postsynaptic by NO synthase, diffuses to the presynaptic where it acticvates guanylyl cyclase and cGMP. Used in coord activités of multiple cells in a small region.

Question 56

What gases can be a retrograde signal?

Answer 56

NO and CO.

Question 57

What are endocannabinoids?

Answer 57

Small lipids which reduce GABA release at inhibitory terminals.