Neuro3 - Neurones & Glia

Question 1

3 types of glial cells (neuroglia)

Answer 1

1. ) Astrocytes - supporting cells
   - several different types and most abundant glial cell
2. ) Oligodendrocytes - myelinates axons in CNS
   - wraps around multiple axons simultaneously
3. ) Microglia - macrophages in the CNS, APC to T cells
   - CNS is considered ‘immune privileged’, it can inhibit the initiation of the pro-inflammaotry T-cell response
   - rigid skull cannot tolerate volume expansion

Question 2

5 functions of astrocytes

Structural
Energy
Re-Uptake
Buffering
Blood-Brain Barrier

Answer 2

1.) Structural Support

2. ) Provide Energy - produces lactate from glycogen
   - supplements the neurone’s supply of glucose
   - uses the glucose-lactate shuttle to transport glucose from blood to the neurone
3. ) Neurotransmitter Re-Uptake - from the synpase
   - have transporters for transmitters like glutamate
   - this helps prevent excito-toxicity
4. ) Buffers Potassium Ions - takes up K+ from the ECF
   - high neuronal levels increases [K+] which can causes inappropriate depolarisations in the brain ECF
5. ) Helps Form the Blood-Brain Barrier
   - end feet of astrocyte processes

Question 3

3 features of the blood-brain barrier (BBB)

Function
3 features of Brain Capillaries
Pathways across the BBB x2

Answer 3

1.) Function - limits diffusion of substances from blood to the brain ECF to maintain environment for neurones

2. ) Brain Capillaries - special features to maintain BBB:
   - tight junctions between endothelial cells
   - basement membrane surrounding capillary
   - end feet of astrocyte processes
3. ) Pathways across the BBB
   - water and CO2 can freely diffuse across the BBB
   - glucose, AAs, ions need transporting across, allowing their concentrations to be easily controlled

Question 4

3 types of neurotransmitters in the CNS

Amino Acids x3
Biogenic Amines x5
Peptides x6

Answer 4

1. ) Amino Acids - excitatory or inhibitory
   - glutamate is excitatory (>70% of all CNS synapses)
   - GABA is inhibitory in the brain
   - glycine is inhibitory in the brainstem and spinal cord
2. ) Biogenic Amines - mostly act as neuromodulators
   - ACh, NA, dopamine, serotonin, histamine

3.) Peptides - somatostatin, cholecystokinin, substance P, neuropeptide Y, dynorphin, enkephalins

Question 5

2 types of glutamate receptors

Ionotropic x3
Metabotropic (2 actions)

Glutamatergic Synapses

Answer 5

1. ) Ionotropic Glutamate Receptors - activation causes depolarisation (Na+ influx)
   - AMPA and Kainate receptors: permeable to Na+/K+
   - NMDA receptors: Na+, K+, and Ca2+
   - glycine is a co-agonist for NMDA receptors
2. ) Metabotropic Receptors - mGluR1-7 (GPCRs)
   - changes in IP3 and Ca2+ mobilisation (PLC)
   - inhibition of AC and decreased cAMP levels
3. ) Glutamatergic Synapses - have AMPA and NMDA
   - AMPA mediates the initial fast depolarisation
   - NMDA also needs the cell to be depolarised to allow ion flow, (Mg2+ originally blocks the pore)

Question 6

3 features of glutamatergic receptors

Role
Long-Term Potentiation
Excitotoxicity

Answer 6

1. ) Role - learning and memory
   - due to induction of long-term potentiation (LTP)
   - receptors show synaptic plasticity (ability of synapses to strengthen or weaken overtime)
2. ) Long-Term Potentiation - very strong stimulations
   - activation of NMDA and mGluRs can up-regulate AMPA receptors creating stronger stimulation
   - Ca2+ entry is important for induction of LTP
3. ) Excitotoxicity - overactivation of excitatory receptors
   - caused by too much Ca2+ entry through NMDA
   - too much glutamate

Question 7

3 features of inhibitory AA neurotransmitters

GABAa and Glycine Receptors
Enhancing Response to GABA (2 drugs)
Release of Glycine

Answer 7

1. ) GABAa and Glycine Receptors - have Cl- channels
   - Cl- influx –> hyperpolarisation –> less AP firing
   - GABAb are GPCRs w/ a modulatory role
2. ) Enhancing Response to GABA - barbiturates and benzodiazepines can bind to GABAa receptors
   - have sedative and anxiolytic effects so used to treat anxiety, insomina and epilepsy
   - barbiturates have risk of OD, dependence, tolerance

3.) Release of Glycine - by inhibitory interneurones in the spinal cord

Question 8

4 features of acetylcholine as a neurotransmitter

Receptors x2
Cholinergic Pathways in the CNS x3
Role x4
Alzheimer’s

Answer 8

1. ) Receptors - main excitatory and acts on both nictotinic and muscarinic receptors in the brain
   - receptors often present on presynaptic terminals to enhance the release of other transmitters
2. ) Cholinergic Pathways in the CNS
   - neurones originate in basal forebrain and brainstem
   - give diffuse projections to many parts of the cortex and hippocampus
   - also local interneurones e.g. corpus striatum

3.) Role - arousal, learning and memory, motor control

4. ) Alzheimer’s Disease - associated w/ degeneration of cholinergic neurones in the nucleus basalis
   - cholinesterase (AChE) inhibitors alleviates symptoms

Question 9

3 features of dopamine as a neurotransmitter

4 Dopaminergic Pathways in the CNS (and roles)
Parkinson’s Disease
Schizophrenia

Answer 9

1.) Dopaminergic Pathways in the CNS - substantia nigra (SNc)
4 pathways:
- nigrostriatal pathway: motor control
- mesocortical pathway: arousal, mood, reward
- mesolimbic pathway: arousal, mood, reward
- tubero-hypophyseal pathway

2. ) Parkinson’s Disease - associated w/ loss of dopaminergic neurones in the nigrostriatal pathway
   - can be treated w/ levodopa + carbidopa (dopamine therapy)
3. ) Schizophrenia - release of too much dopamine
   - amphetamine releases dopamine and NA which produces schizophrenic-like behaviour
   - anti-psychotic drugs are antagonists for D2 receptors

Question 10

3 features of dopamine therapy

Blood-Brain Barrier (LNAA)
AADC
Carbidopa

Answer 10

1. ) Blood Brain Barrier - dopamine cannot cross the BBB however, its precursor levodopa (L-DOPA) can
   - L-DOPA moves through the LNAA (large neutral AA transporter)
2. ) AADC - aromatic AA decarboxylase (enzyme)
   - converts L-DOPA–>dopamine in brain and periphery

3.) Carbidopa - inhibits AADC in the periphery
- stops dopamine being made in the periphery so the
L-DOPA can enter the brain
- can’t cross the BBB so dopamine is made in the brain

Question 11

4 features of noradrenaline as a neurotransmitter

Receptors
Noradrenergic Pathways (location x2 and distribution x4)
Locus Ceruleus
Depression

Answer 11

1. ) Receptors - same in the brain and periphery
   - GPCRs (alpha and beta adrenoceptors)
2. ) Noradrenergic Pathways in the CNS - originate from cell bodies of neurones located in the pons and medulla
   - distribution: cortex, hypothalamus, amygdala and cerebellum
3. ) Locus Ceruleus - nucleus in the pons producing most of the NA
   - activity increases w/ behavioural arousal
   - amphetamines increases release of NA and dopamine and increases wakefulness
4. ) Depression - may be associated w/ NA deficiency
   - NA has relationship w/ mood and state of arousal

Question 12

4 features of serotonin as a neurotransmitter

Receptors
Serotonergic Pathways in the CNS
Functions x2
SSRIs

Answer 12

1.) Receptors - 5-HT (serotonin receptors)

2. ) Serotonergic Pathways in the CNS
   - originates from Raphe nuclei, projecting rostrally
   - similar distribution to NA neurones

3.) Functions - sleep/wakefulness, mood

4. ) SSRIs - serotonin selective reuptake inhibitors
   - treatment of depression and anxiety disorders