2.1 Neurones And Glial Flashcards

1
Q

What is the general role of glia in the CNS?

A

Support, nourish and insulate neurones and remove waste

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2
Q

Name three types of glial cells (neuroglia)

A

Astrocytes
Oligodendrocytes
Microglia

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3
Q

What is the role of astrocytes?

A
  • Structural support
  • Help provide nutrition for neurones (glucose-lactate shuttle)
  • Remove neurotransmitter (uptake) so control concentration (especially for glutamate which is toxic)
  • Maintain ionic environment (k+ buffering)
  • Help to form blood brain barrier
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4
Q

How do astrocytes help provide energy for neurones?

A

Neurones do not store or produce glycogen

Astrocytes produce lactate which can be transferred to neurones which supplements their supply of glucose.
This is done via the glucose-lactate shuttle.

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5
Q

How do astrocytes help to remove neurotransmitter

A

Re uptake

  • astrocytes have transporters for transmitter such as glutamate and gaba
  • helps to keep the extracellular concentration low

Need to keep it low so receptors can be deactivated to keep the conduction mechanism going
High glutamate causes Ca entry into neurones which can kill them

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6
Q

How do astrocytes help to buffer K in Brain ECF

A

High levels of neuronal activity could lead to a rise i K in ECF

Astrocytes have very negative membrane potential and can take up chloride ions = helps keep a low K conc outside as they take a K in with them

Astrocytes are connected to one another so K can move from one astrocyte to another to help maintain low Ca conc

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7
Q

How can high potassium in the ECF be toxic to neurones

A

Potassium gets to high, will depolarise surrounding neurones = get lots of conduction between neurones = lots of glutamate = lots of ca enters neurones = TOXIC TO NEURONES

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8
Q

What are Oligodendrocytes

A
  • responsible for myelination of axons in CNS

- Compare with PNS where Schwann cells are responsible for myelination

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9
Q

What are micro glial?

A
  • Immunocompetent cells
  • Recognise foreign material - activated
  • Phagocytosis to remove debris and foreign material
  • Brains main defence system

they have a mesodermal origin (other cells have ectodermal origin)

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10
Q

what is the function of the blood brain barrier?

A

limits diffusion of substances from the blood to the brain extracellular fluid = helps maintain a correct environment for neurones in brain ECF

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11
Q

what forms the blood brain barrier and what are its components?

A

formed by endothelial cells of capillaries
brain capillaries have
- tight junctions between endothelial cells
- basement membrane surrounding capillary
- end feet of astrocyte processes

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12
Q

why is blood not a suitable environment for neurones?

A

contains things e.g amino acids which can act as neurotransmitters
furthermore, can get K levels in blood increasing = not good for neurones etc

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13
Q

what substances can cross the blood brain barrier?

A

glucose, amino acids and potassium

this allows conc to be maintained and controlled on both sides of the barrier

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14
Q

how is the CNS immune privileged?

A

in the way its specialised

  • has microglia to act as antigen presenting cells
  • T cells can enter the CNS
  • Rigid skull will not tolerate volume expansion = too much inflammatory response would be harmful, therefore CNS inhibits initiation of pro inflammatory T cell response
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15
Q

how is neurotransmitter released at the synapse?

A

depolarisation in the terminal opens voltage gated Ca channels. Ca ions enter the terminal

vesicles fuse and release transmitter

neurotransmitter diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane

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16
Q

name 3 amino acid derived neurotransmitters and whether or not the are excitatory or inhibitory

A

glutamate - excitatory (main one)
GABA - inhibitory (main one in brain)
glycine - inhibitory (main in brainstem and spinal cord)

17
Q

name 5 biogenic amines that act as amino acids

A
acetylcholine - mainly excitatory in brain
noradrenaline
dopamine
seratonin 
histamine
18
Q

name 2 peptide neurotransmitters

A

somatostatin

cholecystokinin

19
Q

what are the ionotropic glutamate receptors?

A

AMPA receptors (mediate initial fasr depolarisation)
Kainate receptors
NMDA receptors

all Na/K (NMDA also has Ca)

activation causes depolarisation = get depolarised = increased excitability

20
Q

what is a metabotropic glutamate receptor?

A

Has a GPCR response

e.g mGluR1-7

linked to either

  • changes in IP3 and Ca mobilisation
  • inhibition of adenylate cyclase and decreased cAMP levels
21
Q

what are the action potentials like in a excitatory post synaptic potential?

A

depolarisation via ligand gated ion channels causes more action potentials

22
Q

how do NMDA receptors work?

A

they are glutamatergic, inotropic receptors

permeable to Na/K and also Ca

need glutamate to bind and the cell to be depolarised to allow ion flow through the channel
(glycine acts as a co- agonist)

  • activation of NMDA (and mGluRs) can up regulate AMPA receptors
  • strong, high frequency stimulation causes long term potentiation
  • Ca entry through NMDA receptors is important for induction of LTP
23
Q

what is long term potentiation?

A

Long-term potentiation (LTP) is a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.

24
Q

How can too much glutamate cause excitotoxicity via NMDA receptors?

A

receptors open = too much Ca enters = get excitoxicity

25
Q

how do GABA(A) and glycine receptors cause an inhibitory post synaptic potential?

A

thye have integral Cl channels
opening these channels causes hyper polarisation
= inhibitory post synaptic potential
= decreased action potential firing

26
Q

what is the role of GABA(b) receptors?

A

they are GPCRs and have a modulatory role

27
Q

what drugs can enhance the response to GABA?

A

Barbiturates

  • anxiolytic and sedative actions
  • risk of fatal tolerance and dependance
  • sometimes used as anti epileptic

benzodiazepines

  • have sedative and anxiolytic effects
  • used to treat anxiety, insomnia and epilepsy
28
Q

where do cholinergic pathways in the CNS originate and what projections do they give?

A

originate in basal forebrain and brainstem

give diffuse projections to many parts of the cortex and hippocampus

there are also local cholinergic interneurones e.g in corpus striatum

29
Q

what are the roles of cholinergic pathways and what can their degradation lead to?

A

roles in arousal, learning and memory, motor control.

degeneration of neurones in the nucleus basalis is associated with Alzheimers disease (can use cholinesterase inhibitors to alleviate the symptoms of Alzheimers)

30
Q

how can Parkinson’s be treated with levodopa?

A

parkinsons = associated with a loss of dopaminergic neurones, especially substantial nigra input to the corpus striatum

so, levodopa, a precursor of dopamine, is converted to dopamine by DOPA decarboxylase

31
Q

what is the relationship between schizophrenia and dopamine?

A

release of too much dopamine

antipsychotic drugs are antagonists at dopamine D2 receptors

32
Q

how does dopamine therapy with levodopa work?

A

Levodopa transported across the blood brain barrier and converted into dopamine by AADC (aromatic amino acid decarboxylase) enzyme.

also give Carbidopa with Levodopa. Carbidopa cannot cross the blood brain barrier unlike levodopa. Carbidopa will inhibit AADC on the periphery side of the blood brain barrier to prevent any levodopa being converted into dopamine before it enters the brain = get max amount of dopamine in brain

33
Q

where does most NA in the brain come from?

A

a group of neurones in the locus ceruleus

  • LC neurones inactive during sleep
  • activity increases during behavioural arousal
34
Q

what are the functions of serotonin as a neurotransmitter?

A

functions

  • sleep/wakefulness
  • mood

NB: SSRIs = serotonin selective reuptake inhibitors, treatment of depression and anxiety disorders