The Role of Neurones and Glia

Question 1

An important source of dopamine for the motor system can be found in which structure?

Answer 1

Substantia nigra

Question 2

Which cell type can assume a macrophage-like appearance when activated?

Answer 2

Microglia

Question 3

Which cell type is primarily responsible for maintenance of the BBB?

Answer 3

Astrocytes

Question 4

What are the peripheral side effects of L-DOPA?

Answer 4

Tend to be GI related

• nausea
• anorexia

Question 5

How are the side effects of L-DOPA ameliorated by giving carbidopa?

Answer 5

1) L-DOPA to dopamine by AADC (aromatic amino acid decarboxylase)
2) increased dopamine = GI side effects
3) carbidopa inhibits AADC = decreased side effects

Question 6

What is the somatic nervous system?

Answer 6

Part of the peripheral NS

Responsible for voluntary muscle and reflex arc

Question 7

What is the autonomic nervous system?

Answer 7

Parasympathetic and sympathetic NS

Controls bodily functions not consciously directed

Question 8

What structures are in the peripheral NS?

Answer 8

Dorsal and ventral roots

Spinal nerves

Peripheral nerves

Question 9

What structures are in the central NS?

Answer 9

Cerebral hemispheres

Brainstem and cerebellum

Spinal cord

Question 10

Describe the blood supply of the brain

Answer 10

Anterior, middle and posterior cerebral arteries

Question 11

Describe the cranial meninges

Answer 11

Dura mater - tough fibrous layer, adhered to bone (periosteal, meningeal)

Arachnoid layer - CSF present in subarachnoid space

Pia mater

Question 12

What types of glia cells exist in the nervous system?

Answer 12

Astrocytes

Oligodendrocytes

Microglia

Question 13

Astrocytes

Answer 13

Most abundant glial cell

Structural support

Provide nutrition for neurones = glucose-lactate shuttle

Remove excess neurotransmitters = important for glutamate as its toxic

Though K+ buffering = maintain ionic environment

Help form BBB

Question 14

How do astrocytes provide energy for neurones?

Answer 14

Astrocytes supplements their supply of glucose

2 lactate is produced and transferred into the neurone

Lactate is then transformed into pyruvate

Question 15

Why do astrocytes need to buffer K+?

Answer 15

High levels of neuronal activity = [K+] rise in brain ECF

Astrocytes take up the K+ to prevent this

Otherwise would change the pH and damage neurones

Question 16

What cell type myelinate in the CNS vs the PNS?

Answer 16

CNS = oligodendrocytes

PNS = schwann cells

Question 17

Outline the role of oligodendrocytes

Answer 17

Insulators

Responsible for myelinating the CNS

Question 18

Describe microglia

Answer 18

Immunocompetent cells

Recognise foreign material = activated = change shape = phagocytose

Can act as APCs and present Ags to T cells that can enter the CNS

Question 19

What is the role of the blood brain barrier?

Answer 19

Limits diffusion from blood to brain extracellular fluid = maintain environment for neurones

Formed by tight junctions between endothelial cells in the capillary, surrounded by astrocytes

Question 20

What substances are transported across the BBB?

Answer 20

Glucose

AA

K+

Question 21

What substances can get freely through the BBB?

Answer 21

H2O

O2

CO2

Hormones

Question 22

How does the immune system in the CNS vary from the immune response in the rest of the body?

Answer 22

CNS inhibits initiation of pro-inflam T cell response = don’t want to much inflam in a bone box

Does not undergo rapid rejection of allographs

Question 23

Outline the structure of a typical neurone

Answer 23

Cell soma

Dendrites

Axon

Terminals

Question 24

Describe the neruotransmitter release

Answer 24

Depolarisation in terminal = opens voltage-gated Ca2+ channels = Ca2+ ions enter terminal

Vesicles fuse = release transmitter

Neurotransmitter diffuses across the synaptic cleft = binds to receptors on postsynaptic membrane

Question 25

What types of receptors can be present on the postsynaptic membrane?

Answer 25

Ligand-gates GPCR

Question 26

What are the 3 main classes of neurotransmitters?

Answer 26

AA Biogenic amines Peptides

Question 27

Describe AA neurotransmitters

Answer 27

Excitatory AA = glutamate Inhib AA = GABA, glycine

Question 28

How can glutamate receptors be classified?

Answer 28

Ionotropic = ion channels permeable to Na+/K+, activation causes depolarisation Metabotropic = GPCR, changes in IP3 or inhib of adenylate cyclase

Question 29

Explain glutamate receptors role in learning and memory

Answer 29

Activation of NMDA receptors (and mGluRs) can up-regulate AMPA receptors(initial fast depolarisation) Strong, high frequency stimulation causes long term potentiation (LTP) Ca2+ entry through NMDA receptors important for induction of LTP

Question 30

Where are inhibitory AA neurotransmitters found?

Answer 30

GABA – brain Glycine – brainstem and spinal cord

Question 31

Explain how GABA and glycine receptors are inhibitory

Answer 31

GABA and glycine receptors have Cl channels Open Cl = hyperpolarisation = inhibitory post-synaptic potential = decreased AP

Question 32

What drugs enhance the response to GABA?

Answer 32

Barbiturates = anti-epileptic Benzodiazepines = sedative, anxiolytic

Question 33

What biogenic amines exist?

Answer 33

Acetylcholine Dopamine Noradrenaline Serotonin (5-HT) mostly act as neuromodulators confined to specific pathways

Question 34

What is the role of acetylcholine as a neurotransmitter?

Answer 34

neuromuscular junction ganglion synapse in ANS postganglionic parasympathetic

Question 35

Outline the cholinergic pathways in the CNS

Answer 35

Pathway arising the the nucleus basalis (first to die in Alzheimer’s) Projects throughout the cerebral cortex Septal neurones projecting into the hippocampus (LTP) Involved in arousal , learning & memory

Question 36

Outline the dopaminergic pathways in the CNS

Answer 36

Substantia nigra (first to die in parkinsons) to striatum involved in motor control Mesolimbic pathway to amygdala and hippocampus – control of mood, arousal, reward

Question 37

What conditions are associated with dopamine dysfunction?

Answer 37

Parkinson’s = loss of dopaminergic neurones, treat: levadopa converted to dopamine Schizophrenia = too much dopamine, treat: antagonists at dopamine D2 receptors

Question 38

Outline noradrenaline as a neurotransmitter

Answer 38

transmitter at postganglionic – effector synapse in ANS Also acts as a neurotransmitter in the CNS Operates through G protein-coupled α- and β-adrenoceptors

Question 39

Outline the noradrenergic pathways in the CNS

Answer 39

Locus coeruleus contain noradrengeneric neurones (pons/medulla) Diffuse release of NA throughout

Question 40

Outline how noradrenaline effects behavioural arousal

Answer 40

Locus ceruleus inactive during sleep Activity increases during behavioural arousal Depression associated with deficiency of NA

Question 41

Where does noradrenaline come from?

Answer 41

NA comes from neurones in the locus ceruleus

Question 42

Outline the serotonergic pathways in the CNS

Answer 42

Serotonin from the raphe nuclei to the rest of the brain Function: sleep/wakefulness, mood

Question 43

What can be used for the treatment of depression and anxiety disorders

Answer 43

SSRIs = selective serotonin reuptake inhibitors