Neurones And Glia Flashcards
Astrocytes main functions
Structural support - (processes envelope CNS axons asvwell as presence of intercellular junctions between astrocytes)
• Help to provide nutrition for neurones
– glucose-lactate shuttle
If there is low supply of glucose astrocytes can provide energy. Neurones do not store glycogen by astrocytes do. Convert glycogen into lactate which is transferred to neurone and converted to pyruvate which releases ATP.
• Reuptake neurotransmitters
Astrocytes have transporters for the neurotransmitters and help keep extracellular conc low. Allows synaptic response to be terminated. (especially important for glutamate - toxic)
• Maintain ionic environment
– K+ buffering in brain ECF.
High levels of neuronal activity could lead to a rise in [K+] in brain ECF.
This is because during action potential Na+ moves in and K+ out.
Inc in K+ conc = depolarise neurones - positive feedback loop.
Astrocytes take up K+ to prevent this though K+ ions channels and Na+/K+ATPase. Also coupled with one another so ions can move between them.
• Help to form blood brain barrier - Induce expression of tight junctions between brain endothelial cells
Some other
o Can react to CNS trauma, helping to form scar tissue and to repair damage
o Connected to each other via gap junctions which is thought to form a syncytium (calcium waves can
propagate through this, which might contribute to cognitive function)
o It is also known that astrocytes take part in synaptic function (the so called tripartite synapse)
Astrocyte has receptors for neurotransmitter. Interneurons synapse with astrocyte sat BBB.
• Has a role in many CNS diseases including stroke and tumours
Oligodendrocytes
▪ Relatively small cells with many processes
▪ Myelinate CNS axons (PNS axons by Schwann cells).
• One oligodendrocyte myelinates multiple axons
▪ Damaged in multiple sclerosis
Microglia
Brain’s main defence
Immunocompetent cells Recognise foreign material - activated - long dendrites swell - becomes phagocytic cell.
• Phagocytosis to remove debris and foreign material
BBB
Function:
Maintains correct environment for neurones
Limits diffusion of substances from blood to brain ECF
Tight junctions between endothelial cells of capillaries forms BBB.
Brain capillaries have:
Tight junctions
Basement membrane Astrocyte processes end feet
CO2 and O2 freely diffuse
Glucose has to be transported through GLUT 1.
N+ and K+ transported through ion channels.
Amino acids need to be transported.
Immune privileged
Does not undergo rapid rejection of allografts as inflammatory response would inc ICP. Inhibits pro-inflammatory T-cell response.
Does undergo rejection if allograft is some other part of body.
Microglia act as APC
T-cells can enter CNS
Neurotransmission
Chemical classes of neurotransmitters
Amino acids - glycine, glutamate, GABA
Biogenic amines - Ach, noradrenaline, dopamine, histamine, serotonin (5-HT)
Peptides - cholecystokinin, somatostatin, neuropeptide Y
Excitatory - Glutamate
Glutamate receptors
Ionotropic - ion channels permeable to Na+, K+
Kainate
AMPA
NMDA - also permeable to Ca2+. Blocked by Mg2+. Need glutamate to bind and cell to be depolarised to allow ion flow. Glycine acts as co-agonist.
Activation causes depolarisation- inc excitability
Metabotropic - mGluR1-7
G protein-coupled receptor
Linked to changes in IP3 and Ca2+ mobilisation
Or inhibition of Adenylate cyclase and dec cAMP
excitatory response
Fast excitatory response:
RMP - -60mV
Glutamate
AMPA (ligand-gated) mediates initial fast depolarisation and NMDA also present (need activation through AMPA and cell to be depolarised to allow ion flow)
Depolarisation
AP
Learning and memory:
Activation of NMDA receptors can upregulate AMPA receptors
Strong, high-frequency stimulation causes long term potentiation due to
Ca2+ entry through NMDA. This is how learning and memory happens.
Can also have long term depressed- synapses regulated in a downward fashion.
Too much Ca2+ entry kill neurones - excitotoxcity.
Inhibitory response
RMP - -60
GABA and glycine have integral Cl- channels
Open Cl- channels
Hyperpolarisation + inhibitory post-synaptic potential
Dec AP firing
GABA has G-protein coupled receptors as well.
GABA inc effect
Inc inhibitory effect of GABA by binding to GABA A receptors - barbiturates (not used anymore due to fatal overdoses) and benzodiazepines
Sedative and anxiolytic action
Used for insomnia, anxiety, epilepsy.
Glycine example
Glycine Present in spinal cord and brainstem
Stretch reflex when you hit patellar tendon:
Stretch of quadriceps muscle
Sensed by muscle spindle
Afferent neurone to spinal cord - excitatory - releases glutamate
Activates motor neurone
Go to quadriceps -release Ach - contract
In spinal cord afferent neurone also acts on interneurone by releasing glutamate
Interneurone releases glycine which acts on efferent neurone for hamstrings
Hamstrings relax
Ach in the CNS
Discrete group of neurones in basal forebrain - nucleus basalis - project throughout cerebral cortex and hippocampus (learning + memory). First to degenerate in Alzheimer’s. Cholinesterase inhibitors used to alleviate symptoms.
Local cholinergic interneurones in the corpus striatum, substantia niagra and thalamus.
Involved in arousal, learning & memory, motor control
Dopamine in CNS
Nigrostriatal pathway involved in motor control
Midbrain to cortex - mesocortical pathway - arousal
Mesolimbic pathway- to amyglada and hippocampus - arousal
Parkinson’s
Loss of dopaminergic neurones
Substantial niagra to corpus striatum pathway
Treated by levodopa (precursor to dopamine) - transported across BBB - converted by DOPA decarboxylase.
DOPA decarboxylase is also in periphery so give carbidopa (cannot cross BBB so does not inhibit in brain) to inhibit conversion in periphery.
Schizophrenia - too much release of dopamine
Amphetamines release dopamine and noradrenaline- produces schizophrenic like behaviour
Antipsychotic drugs are antagonists to D2 receptors
Noradrenaline in CNS
G protein-coupled alpha and beta adrenoreceptors
Discrete group of cell bodies of NA contains neurones in pons and medulla called locus coeruleus - diffuse projection to cortex, cerebellum, hypothalamus, amyglada(mood and reward)
Also project down spinal cord
Behavioural arousal
Locus coeruleus inactive during sleep
Activity increases during behavioural arousal
Amphetamine inc release of NA and dopamine and inc wakefulness
Depression may be linked with deficiency of NA
