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Principles of CNS Biochemistry Flashcards

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1
Q

What is synaptic neurotransmission?

A

The release of neurotransmitters into the synaptic cleft which can induce an inhibitory or excitatory effect on post-synaptic receptors

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2
Q

What are neurotransmitters?

A

Neurotransmitters are chemicals used for neuron communication in the synapatic cleft.

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3
Q

What are the types of neurotransmitters?

A

Neurotransmitters are divided into small neurotransmitters and neuropeptides.

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4
Q

What are small neurotransmitters?

A

Small neurotransmitters are synthesised in the presynpatic terminal and packaged in clear small vesicles. They modulate fast synaptic transmission

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5
Q

Where are small neurotransmitters synthesised?

A

In the presynaptic terminal

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6
Q

Where are the enzymes that metabolise small neurotransmitters synthesised?

A

In the soma

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7
Q

What are peptide neurotransmitters?

A

Short chain polypeptides which are stored as large vesicles in the presynaptic neuron. It is synthesised along with the enzyme metabolisers in the soma and transported down the axon. They modulate ongoing synapatic activity and slow synaptic transmission.

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8
Q

Which receptors do neuropeptides act on?

A

G protein-coupled receptors which are metabotropic and induces secondary messanger response.

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9
Q

Which physiological processes are neuropeptides involved in?

A

Secretion of salivary fluid, gastric fluid, intestinal fluid and electrolytes.

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10
Q

How are neuropeptides synthesised?

A

In the soma from precursor proteins through selective cleavage by enzymes

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11
Q

Which pathologies are associated with neurotransmitter function?

A

Alzheimer’s disease, Parkinson’s disease, Schizophrenia and Depression.

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12
Q

What are the classes of small neurotransmitters?

A

Biogenic amines, small amines and gases and aCH

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13
Q

What are the biogenic amines?

A

Catecholamines, serotonin and histamine.

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14
Q

What are the amino acid neurotransmitters?

A

Glutamate, GABA and glycine.

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15
Q

What are the gas neurotransmitters?

A

NO and CO. These are synthesised and released immediately following action potential and are not stored in vesicles so they are not released by exocytosis.

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16
Q

What are examples of large neuropeptides?

A

Substance P, endorphins, somatostatin and vasopressin.

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17
Q

What is co-transmission?

A

The exocytosis of multiple separate vesicles due to the frequency of stimulation. Low frequency means there is multiple exocytosis of small vesicles. High frequency has multiple exocytosis of small and large vesicles.

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18
Q

What is co-release?

A

The release of a vesicle containing more than one type of neurotransmitter.

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19
Q

What is the criteria for chemical messenger to be a neurotransmitter?

A

It must be synthesised or present in the neuron. It must produce a response when bound to receptors on target cell l to continue the signal. It should have the same response when attached directly to the target cell. It must be removed from synaptic cleft.

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20
Q

What is a catecholaminergic neuron?

A

A neuron which releases dopamine, adrenaline or noradrenaline.

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21
Q

Which receptors do neurotransmitters of the nervous system act on?

A

Ionotropic and metabatatropic.

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22
Q

What are ionotropic receptors?

A

They are ligand gated ion channels composed of multiple subunits which open in response to ligand binding on allosteric site and allow influx of ions which cause a change in the membrane potential and generates a response

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23
Q

What are metabotropic receptors?

A

G protein coupled receptors which respond to binding of neurotransmitter by activating G protein to induce second messanger activation or activate an ion channel.

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24
Q

What type of receptor is muscarinic?

A

Metabotropic/ G protein coupled cholinergic receptor associated mainly with the parasympathetic nervous system and found in the peripheral tissues of glands and smooth muscles.

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25
What type of receptor is nicotninic receptor?
Ionotropic/ligand gated ion channel cholinergic receptor associated with the sympathetic and parasympathetic nervous system
26
What is acetylcholine?
A small neurotransmitter important in the cerebral cortex and the hippocampus for modulating fast-synapatic transmission by co-ordinating neuronal firing and synaptic plasticity.
27
What are sweat glands?
Muscarinic metabatropic receptors part of the sympathetic nervous system.
28
What system is the muscarininc receptor involved in?
Muscarinic receptor which acts on peripheral tissues and glands and is involved mainly in the parasympathetic system. Muscarinic receptor are present in the sweat glands, intestines for gut motility, smooth muscle of the heart for relaxation and CNS.
29
Which sympathetic response is muscarininc receptor invovled in?
The only sympathetic Muscarinic receptor are present in the sweat gland for secretion.
30
Which division of the autonomic nervous system are nicotinic receptors involved in?
Nicotininc receptor are involved in the sympathetic and parasympathetic response. It is present in the neuromuscular junction, sympathetic chain ganglia, adrenal chromaffin cells and the parasympathetic postganglionic neurons.
31
What is Alzheimer's disease and treatment?
Neurodegenerative disease with depletion of acetylcholine due to build up of protein deposits in the brain that forms plaque. This creates issues with the hippocampus and the cerebral cortex involved in memory and cholinergic innervation. There is depletion of glutamate
32
What is the prevalence of Alzheimer's disease?
More prevalent in those over 80, with 20% total. 5% in those over 60.
33
How is acetycholine synthesised?
Choline + acetylcoA -> acetylcholine, catalysed by choline acetyltransferase (CHAT
34
How is acetylcholine metabolised?
Acetylcholine -> choline + acetic acid, catalysed by acetylcholinesterase.
35
Which drugs affect the acetylcholinesterase?
It is inhibited by pyridostigmine, in order to increase depleted levels of AcH associated with glaucoma, myasthenia gravis and Alzhiemer's disease.
36
What are the types of nicotinic receptors?
Two types: Nictonic Nn and Nicotinic Nm
37
Where are Nicotinic Nn found?
In the post sympathetic ganglia and the presynaptic cholinergic memory. They mediate fast neurotransmission.
38
Where are Nicotinic Nm found?
In the skeletal motor end plate of the NMJ
39
What are the types of muscarinic receptors?
M1, M2, M3, M4, ,M5
40
Which muscarinic receptors are coupled to G protein/phospholipase C?
M1, M3 and M5 which induces the secondary messanger phospholipase C. M1 is found in the cortex, These are found in the brain and the heart.
41
Which muscarinic receptors are coupled to G protein-> open K+ ion channels?
M2 which is in the heart and and M4 which is found in the basal ganglial, hippocampus and thalamus.
42
What are the essential amino acid neurotransmitters derived from the diet?
Glutamate, glycine and GABA.
43
What is glutamate?
Amino acid excitatory neurotransmitter which is principal neurotransmitter of the brain.
44
How is glutamate synthesised?
From Glutamine -> GLutamate, catalysed by glutaminase enzyme. It can also be synthesised from transamination of 2-oxo-glutarate, a product of the TCA cycle.
45
How is glutamate metabolised? .
Reuptake by pre-synaptic cell or taken up by peptide transporters into glial cells, where glutamate is converted ->glutamine by glutaminase enzyme
46
Which pathologies are linked to low glutamate?
Motor neurone disease, epilepsy and Alzhiemer's disease and schizophrenia
47
What are the types of glutamate receptors?
Glutamate receptors are ionotropic and modulate fast-synaptic transmission for synaptic plasticity in the CNS. There are 3 glutamate receptors: AMPA, NMDA and Kainate
48
What is the AMPA receptor?
Ionotropic glutamate receptor which is activated and causes influx of Na+ into the cell for depolarisation. It modualtes fast-synaptic transmission and synaptic plasticity.
49
What is the NMDA receptor?
Ionotropic excitatory glutamate receptor which is activated by binding of both glutamate and glycine. NMDA releases Mg2+ due to cell depolarisation and allow influx of Ca2+. NMDA modulates fast synapatic activity in the brain and synaptic plasticity for memory formation
50
What is the Kainate receptor?
Glutamate ionotropic receptor which modulates fast synaptic activity in the brain and synaptic plasticity.
51
Which pathology is associated with glutamate NMDA receptor?
Epilepsy
52
Which neurons are synaptic excitatory in the brain?
Glutamate
53
Which neurons in the brain are synapatic inhibitory?
GABA and glycine
54
How is GABA synthesised?
From glutamine. Glutamine is converted -> glutamate by glutaminase. Glutamate is converted -> GABA by GABA decarboxylase.
55
How is GABA metabolised?
GABA is either re-uptake by the presynaptic cell or it its taken up by glial cells via transporters. GABA is metabolised -> glutamate by Glutamate decarboxylase and glutamate -> glutamine by glutaminase enzyme
56
What is the GABA receptor?
Ionotropic receptor with pentameric structure of alpha, beta, gamma/delta subunits
57
How does GABAmergic transmission occur?
GABA is released via exocytosis and it binds to the GABA receptor to induce opening of the channel and influx of CL-. It is a synaptic inhibitory neurotransmitter so influx of CL- causes hyperpolarisation of the cell.
58
How is anxiety treated?
Using Valium/ benzodiezapam. This is a GABA agonist which acts on the receptor to induce CL- influx for hyperpolarisation
59
What is epilepsy?
Epilepsy is uncontrolled electrical activity in the brain due to imbalance between excitatory neurotransmitters (glutamate) and inhibiotry neurotransmitters (GABA). It can be treated using diazepam to increase GABA receptor agonism or sodium valproate which increases quantity of GABA
60
What is sodium Valproate?
A drug which increases levels of GABA in the brain for increased synaptic inhibition. It is used as a treatment for epilepsy.
61
How is epilepsy treated?
Diezapam or sodium valproate.
62
What is barbiturate?
Enhances GABA effect by binding to the subunit of GABA receptor and increasing duration of its opening for CL- to increase hyperpolarisation.
63
What is glycine?
A synaptic inhibitory neurotransmitter which is present in the brainstem nuclei and spinal cord to modulate motor and somatosensory systems.
64
How is glycine synthesised?
Serine is converted -> glycine by SHMT enzyme.
65
How is glycine metabolised?
It is metabolised in astrocytes from glycine -> CO and NH3 or undergoes reuptake by the pre-synaptic neuron
66
What is hyperekplexia?
Hereditary condition caused by defective glycine channel which causes hypertonia and inappropriate exaggerated reaction to stimuli.
67
What is strychnine?
Anticonvulsant through acting as glycine antagonist.
68
How does transmission occur from the cortex to the motor neuron of the spinal cord?
Glutamergic excitatory neuron from cerebral cortex synapses with the ventral horn of the spinal cord and acts on the alpha motor neuron to release acetylcholine. This motor neuron is modulated by the reccurrant inhibitory glycinergic interneurone, via the recurrant branch.
69
What is the neurotransmitter of the motor pathway?
Glutamate
70
What is the neurotransmitter of the motor neuron?
Acetylcholine
71
What is a Renshaw cell?
Inhibitory interneuron which modulates motor neuron via recerrant branch connection
72
What are the catecholamines?
Adrenaline, noradrenaline and dopamine which all contain the catechol group.
73
Where is dopamine synthesised?
In the pre-synaptic terminal from tyrosine that travels across the blood-brain barrier.
74
What do catecholaminergic neurons contain?
Tyrosine hydroxylase.
75
How are catecholamines synthesised?
Via tyrosine Kinase. Tyrosine Kinase is converted to -> L-DOPA via tyrosine hydroxylase. L-DOPA is converted into dopamine via DOPA decarboxylase. Dopamine then forms -> noradrenaline via Dopa B-hydroxylase. Noradrenaline forms > adrenaline via N-methyltransferase.
76
How are catecholamines inactivated?
Via uptake from the pre-synaptic neuron, diffusing away form the receptor or being metabolised by the enzymes MAO or COMT.
77
What is MAO?
Monoamine oxidase (MAO) metabolises serotonin and the catecholamines such as dopamine. It is present in the outer mitochondria membrane.
78
What is COMT?
Metabolises catecholamines such as dopamine and is present in the liver, kidney and skeletal muscle
79
How is dopamine synthesised?
Via tyrosine Kinase. Tyrosine Kinase is converted to -> L-DOPA via tyrosine hydroxylase. L-DOPA is converted into dopamine via DOPA decarboxylase.
80
What is the mesolimbic pathway?
Dopaminergic pathway for reward and reinforcement
81
What is the mesocortical pathway?
Dopaminergic pathway for planning.
82
What is the nigrostriatal pathway?
Dopaminergic pathway for movement
83
What are the dopamine receptors?
5 dopamine receptors which are classified into D1-like receptors and D2-like receptors
84
What is distinct about D1 and D5?
They are G protein coupled receptors positively coupled to adenylate cyclase for cAMP via Gs protein activation
85
What is distinct about D2, D3 and D4?
D2, D3 and D4 receptors which are negatively coupled to adenylate cyclase to inhibit cAMP VIA Gi activation
86
How does MAO metabolise dopamine?
Dopamine -> DOPAC or Dopamine -> HVA
87
How does COMT metabolise dopamine?
Dopamine -> HVA
88
What is Parkinson's disease?
Degeneration of the substantia nigra which leads to the reduction of dopamine availability. It has a characteristic tremor, rigidity of muscles and shuffling gait. Treated with levadopa to increase dopamine availability however, there is a reduced lack of levadopa availability and schizophrenia like symptoms
89
How is noradrenaline synthesised?
From dopamine -> noradrenaline via dopa B-hydroxylase
90
Where is noradrenaline released from?
Locus coeruleus, a noradrenergic neuron for sleep, waking and attention.
91
What is a noradrenergic neuron?
Locus correleus, part of the reticular activating system for sleep/wake, attention and feeding behaviour
92
What is the implication of increased noradrenaline activity?
Mania
93
What is the implication of decreased noradrenaline activity?
Depression
94
What is the source of tryptophan?
Meat and dairy products
95
What are serotonergic neurons?
Raphe nuclei for sleep, emotion and mood
96
What are the implications of reduced serotonin?
Depression
97
How is serotonin synthesised?
Neurotransmitter synthesised from tryptophan -> by tryptophan decarboxylase. 5-HTP is converted into 5-HT by 5-HT decarboxylase
98
How is serotonin stored?
In pre-synaptic vesicles.
99
What is SERT?
Serotonin transporter for reuptake into the presynaptic cell.
100
What is SSRI?
Inhibits SERT to increase serotonin availability.
101
What is VMAT?
Enzyme which packages serotonin into presynaptic vesicles following pre-uptake or synthesis.
102
What are the serotonin receptors?
Most of the serotonin receptors are metabotropic.
103
What type of receptor is 5-HT3?
Ionotropic receptor.
104
What is a 5-HT1a receptor?
Serotonin receptor in areas of the brain involved in mood, cognition, memory and anxiety.
105
What is Buspirone?
Drug antagonist on presynaptic 5-HT1a to inhibit synthesis and post synaptic as a partial agonist in hippocampus and cortex
106
How is serotonin metabolised by the pineal gland?
Serotonin is metabolised into melatonin to induce sleep.
107
How is serotonin metabolised by MAO?
Serotonin is metabolised into 5-hydroxyindoleacttic acid.
108
How do drugs treat migraine?
Targets the 5-HT1d receptor and 5-HT2
109
What are neuromodulators?
A chemical which enhances the excitatory or inhibitory effect of a receptor by working with neurotransmitters. This includes dopamine and substance P are neuromodulators.
110
What do antidepressant drugs target?
Inhibits MAO to increase serotonin and dopamine availability
111
What do tricyclic drugs?
Increase serotonin and noradrenaline availability by blocking noradrenaline and serotonin reuptake.
112
What is Substance P?
A neuropeptide which is part of the tacykinin family and it is a neuromodulator. of pain perception.
113
What are the receptors of Substance P?
NK1, NK2 and NK3 but it binds strongest to NK1.
114
Where is Substance P found?
In the amygdala, hypothalamus, medulla, substantia nigra. It is present on C fibres.

Year 1 (191 decks)

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