Basic principals of CNS biochemistry

2 main categories of neurotransmitter

• Small molecule neurotransmitter

• Large neuropeptide

Fast synaptic signalling is associated with which kind of neurotransmitter?

Small molecule neuropeptides

Slow synaptic transmission is associated with which type of neurotransmitter?

Large neuropeptides

Where are enzymes for the breakdown of small molecule neurotransmitters produced?

In the nucleus and trafficked to the axon terminal

3 major classes of small molecule neurotransmitters

• biogenic amines

• amino acids

• Gases

Biogenic amines

• Catecholamines (NA, A, dopamine)

• Serotonin (5-HT)

• Histamine

Amino acids

• Glutamate

• GABA

• Glycine

Examples of large neuropeptides

• Substance P

• Endorphins

• Vasopressin

• Oxytocin

Cotransmission

Ability of the neurone to release more than one kind of neurotransmitter

• synaptic vesicles can contain more than one kind of neurotranmitter

Benefit of cotransmission

Gives neurones versatility

5 criteria of a neurotransmitter

• synthesised/present in neurone

• When released must produce response in target cell

• presence of receptor specific to chemical on post synaptic cleft

• Induces same response when placed on target

• must be removed from synaptic cleft

Suffix for naming neurones after the neurotransmitter present

-ergic

• eg: dopaminergic, cholinergic

What are the 2 kinds of receptors?

• Inotropic receptors

• Metabotropic receptors (7 TM receptor with G protein)

Structure of inotropic receptors

• Made up of 3 subunits = variance of receptor

• normally in a closed state but binding = opens channel for passage of ions and action potential

What neurones are involved in the sympathetic branch of the ANS?

• ACh

• Adrenaline

Role of ACh in CNS

• Learning and memory

• Sleep and arousal

• Aggression

• Thermoregulation

Main neurotransmitter effected in alzheimer’s disease?

Acetylcholine (decreases)

2 types of cholinergic receptors - what kind are they?

• nicotinic (inotropic)

• muscarinic (metabotropic)

2 kinds of nicotinic receptors

• Nicotinic N_m

• Nicotinic N_N

Location of nicotinic N_N receptors

Postganglionic neurones, and some presynaptic cholinergic terminals

Location of nicotinic N_M receptors

Skeletal muscle end plates

Location of nicotinic receptors in the body?

• NMJ

• Autonomic ganglia

• Adrenal Medulla

• CNS

Locations of muscarinic receptors in the body

• Peripheral tissues

• ANS

• CNS

5 subtypes of muscarinic receptors

M1

M2

M3

M4

M5

Glutamate - Inhibitory/excitory?

Excitory - half of all neurones on the CNS are glutaminergic

Where does glutamate reuptake occur?

• Into glial cells (where it is broken down into glutamine by glutaminase)

• Or by reuptake receptor transporters in presynaptic membrane

3 kinds of INOTROPIC glutamate receptors

• AMPA

• NDMA

• Kainate

Which glutamate receptor is linked with epilepsy?

NDMA

How does the AMPA glutamate receptor activate the NDMA glutamate receptor?

AMPA = entry of Na+ = cell depolarisation

• this activates the NDMA receptor in presence of glycine

• NDMA ejects Mg2+ and opens channels

• Ca2+ entry activates the secondary messenger model

Where are the reuptake transporters for GABA located?

• On presynaptic terminals

• Glial cells

How is GABA broken down in glial cells?

GABA is broken down into glutamate by GABA transaminase

Glutamate is then broken down into glutamine by glutaminase

Structure of GABA receptors

Pentameric inotropic receptors

GABA - inhibitory/excitory?

Inhibitory

How does GABA cause inhibition?

Influx of Cl- ions into neurone hyperpolarises neurone = inhibition

Main locations of glycine action in the body?

Brainstem and spinal cord

Glycine - inhibitory/excitory?

Inhibitory - linked to Cl- ion channels

What is glycine derived from?

Serine

In what order are catecholamines synthesised from tyrosine?

Tyrosine - L-dopa - dopamine - NA -adrenaline

What enzymes metabolises catecholamines?

MOA or COMT

What are the 3 dopamine systems/ pathways in the brain?

• Mesolimbic (reinforcement)

• Mesocortical (planning)

• Nigrostriatal (movement)

2 kinds of dopamine receptors

• D₁ like (D1 and D5)

• D₂ like (D2,3,4)

What proteins positively couples D₁ like receptors to adenylate cyclase?

G_s proteins

What protein negatively couples D₂ like receptors with adenylate cyclase?

G_i proteins

Source of noradrenaline neurones?

Locus coeruleus

What can an increase in dopamine cause?

Mania

what can a decrease in dopamine cause?

Depression

What 5-HT synthesised from?

Tryptophan

Common sources of tryptophan?

Meat and dairy products

What can a fall in serotonin cause?

Depression

Where is 5-HT stored?

presynaptic vesicles

What mediates serotonin reuptake?

SERT - serotonin transporter

How many subtypes of 5-HT receptors are there?

7

5-HT₁ to 5-HT₇

Which 5-HT receptor is inotropic?

5-HT₃ (rest are metabotropic)