Neurones And Glia Flashcards

1
Q

What are components of the cns

A

• Network of neurones with supporting glia
• Neurones sense changes and communicate with other neurones
– around 1011 neurones
• Glia support, nourish and insulate neurones and remove ‘waste’
– around 1012 glia

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2
Q

What are types of glial cells

A
• Astrocytes (several different types) – most abundant type of glial cell
– Supporters
  • Oligodendrocytes – Insulators
• Microglia
– immune respons
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3
Q

What are the roles of astrocyted

A
• Structural support
• Help to provide nutrition for neurones
– glucose-lactateshuttle
• Remove neurotransmitters (uptake)
– control concentration of neurotransmitters (especially important for glutamate (toxic)
• Maintain ionic environment 
– K+ buffering
• HELP to form blood brain barrier
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4
Q

Hwo do astrocytes provide energy for neurones

A

• Neurones do not store or
•produce glycogen
Astrocytes produce lactate which can be transferred to neurones
• Supplements their supply of glucose
• Glucose lactate shuttle
Lactate used to produce atp
Glycogen can be stored in astrocytes. Can produce pyruvate, lactate. Transporters can transport lactate
Intense neuronal activity - need some more energy (atp) can get lactose lactate shuttel
Can operate for 10-15 min

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5
Q

How do astrocytes help to remove neurotransmitters

A

• Re-uptake
– Astrocyteshave transporters for transmitters such as glutamate
– Helps to keep the extracellular concentration low.

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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 in [K+] in brain ECF
• Astrocytes take up K+ to prevent this
Can get build up of K= in ecf. If it gets too high will depot the surrounding Europe’s - spontaneous electrical activity - too much glutamate - toxic.
Astrocytes perm to cl-, keep memb potential very negative, so they can take upk+ - inward movement of k+ though channels and transporters - work to keep a low k+ conc
Astrocytes can be coupled. So k+ moves between them to maintain low

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7
Q

What are oligodendrocytes

A
  • Responsible for myelinating axons in CNS
  • Compare with PNS where Schwann cells are responsible for myelination
  • Good time to revise ICPP Unit and myelination
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8
Q

What are microglia

A
• Immunocompetent cells
• Recognise foreign material - activated
• Phagocytosis to remove debris and foreign material 
• Brain’s main defence system
Processes get wides when activated 
Mesodermal. Other glia are ectodermal a
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9
Q

What is the bbb

A

• Limits diffusion of substances from the blood to the brain extracellular fluid
• Maintains the correct environment for neurones
• Brain capillaries have
– tight junctions between endothelial cells
– basement membrane surrounding capillary
– end feet of astrocyte processes

Blood is not a suitable environment for neurones as it can have changing levels of, e.g. aas, k+, etc

Endothelial cells from tight junctions- prevents charge molecules difficusing into the brain extracellular space. (Astrocytes do not form bbb but associate)

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10
Q

Describe the pathways across the bbb

A
  • Substances such as glucose and amino acids and potassium are transported across BBB.
  • This allows the concentration to be controlled

Ions or small molecules rely on transporters and channels. Eg glucose in glut1. AAs are transported across - controlwhat crosses over into the brain ecf.

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11
Q

How is the brain immune specialised

A

• Does not undergo rapid rejection of allografts
• Rigid skull will not tolerate volume expansion
– Too much inflammatory response would be harmful - pressure
• Microglia can act as antigen presenting cells
• T-cells can enter the CNS
• CNS inhibits the initiation of the pro-inflammatory T-cell response
• Immune privilege is not immune isolation, rather specialisation

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12
Q

Descrbe neurotransmitter release at the synapse

A
  • Depolarisation in the terminal opens voltage-gated Ca2+ channels. Ca2+ ions enter the terminal
  • Vesicles fuse and release transmitter
  • Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane
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13
Q

Descrbe the postsynaptic response

A

• The response depends on – nature of transmitter
– nature of receptor
• Ligand-gated ion channels
• G-protein-coupled receptors

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14
Q

What are the 3 chemical classes of neurotransmitters

A

AMINO ACIDS
glutamate, GABA, glycine

BIOGENIC AMINES
acetylcholine, noradrenalin dopamine, serotonin (5-HT), histamine,

PEPTIDES
dynorphin, enkephalins, substance P, somatostatin cholecystokinin neuropeptide Y

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15
Q

Descrb amino aid neurotransmitters

A
• excitatory amino acids
– mainly glutamate
– major excitatory neurotransmitter
• over 70% of all CNS synapses are glutamatergic • present throughout the CNS
• inhibitory amino acids – GABA
– Glycine
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16
Q

Desribe glutamate receptors

A

Ionotropic
AMPA Kainate NMDA
receptors receptors receptors Na+/K+ Na+/K+ Na+/K+
and Ca2+
Ion channel - permeable to Na+ and K+ (and in some cases Ca2+ ions)
Activation causes depolarisation – increased excitability
Metabotropic
mGluR1-7
G protein-coupled receptor
Linked to either:
• changes in IP3 and Ca2+ mobilisation
• or inhibition of adenylate cyclase and decreased cAMP levels

17
Q

Describe teh response at glutamate receptors

A

Fast excitatory responses
• Excitatory neurotransmitters cause depolarisation of the postsynaptic cell by
acting on ligand-gated ion channels.
- excitatory postsynaptic potential (EPSP)
- depolarisation causes more action potentials

18
Q

What are the fucntionsof different receptors at glutamierguc synapses

A

• Glutamatergic synapses have both AMPA and NMDA receptors
• AMPA receptors mediate the initial fast depolarisation
• NMDA receptors are permeable to Ca2+
• NMDA receptors need glutamate to bind and the cell to be depolarised to allow ion flow through the channel
– Also glycine acts as a co-agonist
Need ampa to depolarise to activate nomad.

19
Q

Descrive glutamate receptors, synaptic plasticity and excitotoxicity

A

• Glutamate receptors have an important role in learning and memory
– Activation of NMDA receptors (and mGluRs) can up-regulate AMPA
receptors
– Strong, high frequency stimulation causes long term potentiation (LTP)
– Ca2+ entry through NMDA receptors important for induction of LTP
• Too much Ca2+ entry through NMDA receptors causes excitotoxicity – Too much glutamate - excitotoxicity
Lip underlies leaning and memory

Calcium going in - activate downstream signalling - more ampa - more depopulated

20
Q

What are the main inhibitory amino acids

A

• GABA is the main inhibitory transmitter in the brain
GABA
• Glycine acts as an inhibitory neurotransmitter mostly in the brainstem and spinal cord

21
Q

How do gaba and glycine receptors work

A

• GABAA and glycine receptors have integral Cl- channels
• Opening the Cl- channel causes hyperpolarisation
– Inhibitory post-synaptic potential (IPSP)
• Decreased action potential firing

22
Q

How do barbiturates and benzodiazepines affect gaba receptors

A
  • Barbiturates and benzodiazepines bind to GABAA receptors
  • Both enhance the response to GABA - Both modulate the receptors to enhance the action city

– Barbiturates - anxiolytic and sedative actions, but not used for this now
• risk of fatal overdose also dependence and tolerance
• sometimes used as anti-epileptic drugs

– Benzodiazepines
– have sedative and anxiolytic effects
– used to treat anxiety, insomnia and epilepsy

23
Q

Where s glycine in high conc

A

Brainstem ad spinal cord

24
Q

What are bogenic amines and ach

A
  • acetylcholine
  • dopamine
  • noradrenaline
  • serotonin (5-HT)
  • mostly act as neuromodulators • confined to specific pathways
25
Q

Descrbe ach as a neurotransmitter

A
• ACh
– neuromuscularjunction
– ganglion synapse in ANS
– postganglionic parasympathetic
• ACh is also a central neurotransmitter
– acts at both nicotinic and muscarinic receptors in the brain
– mainly excitatory
– receptors often present on presynaptic terminals to enhance the release of other transmitters
26
Q

Wha are cholinergic pathways i the cns

A
  • Neurones originate in basal forebrain and brainstem
  • Give diffuse projections to many parts of cortex and hippocampus (longterm potentiation in hippocampus)
  • There are also local cholinergic interneurones
  • eg in corpus striatum
  • Involved in arousal, learning & memory, motor control
  • Degeneration of cholinergic neurones in the nucleus basalis is associated with Alzheimer’s disease
  • Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease
27
Q

Describe dompanimeric pathways in the cns

A

Nigrostriatal pathway involved in movement control eg in Parkinson’s
Mesocortical pathwats - mood arousal and reward
Also tubero hypophyseal pathway

28
Q

What are conditions associated with dopamine dysfunction

A

• Parkinson’s disease
– associated with loss of dopaminergic neurones
– substantia nigra input to corpus striatum
• Can be treated with levodopa - converted to dopamine by DOPA decarboxylase (AADC)
• Schizophrenia
• May be due to release of too much dopamine
– amphetamine releases dopamine & noradrenaline
– produces schizophrenic like behaviour
– antipsychotic drugs are antagonists at dopamine D2 receptors
– Other neurotransmitters also implicated

29
Q

Descirb dopamine and the bbb

A

Ss

30
Q

Describe NA as a neurotransmitter

A
  • Noradrenaline - transmitter at postganglionic – effector synapse in ANS
  • Also acts as a neurotransmitter in the CNS
  • Operates through G protein-coupled α- and β-adrenoceptors
  • Receptors to noradrenaline in the brain are the same as in the periphery
31
Q

Describe Na pathways in the cns

A

Cell bodies of NA containing neurones are located in the brainstem (pons and medulla)
Diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum

32
Q

Desribe noradrenaline and behavioural arousal

A

• Most NA in the brain comes from a group of neurones in the locus ceruleus
– LC neurones inactive during sleep
– activity increases during behavioural arousal
– amphetamines increases release of noradrenaline and dopamine and increase wakefulness
• Relationship between mood and state of arousal
– depression may be associated with a deficiency of NA

33
Q

Describe serotonergic pathways

A
Serotonin, 5-HT
• Similar distribution to noradrenergic
neurones
FUNCTIONS
• Sleep/wakefulness 
• Mood
• SSRIs (serotonin selective reuptake inhibitors) treatment of depression and anxiety disorders