Glia & Neurotransmitters Flashcards
What are the functions of astrocytes?
- most abundant type of glial cells
- structural support
- provide nutrition for neurones via the glucose-lactate shuttle
- help form the blood-brain barrier
- remove neurotransmitters from synapse (those which are not degraded by enzymes)
- buffer K+ in the ECF of the brain (K+ channels & Na+/K+/2Cl- transporters import K+ —> travel across gap junctions to neighbouring glial cells)
Outline the glucose-lactate shuttle in astrocytes. What is its purpose?
- GLUT1 import glucose into the interstitium (transported into neurones via GLUT3 to be metabolised) and astrocytes
- Glucose & glycogen metabolised into lactate in astrocytes
- MCT1 & MCT2 (H+/lactate transporters) transport lactate and H+ from astrocytes into neurones
- Lactate metabolised in neurone
Neurones do not produce or store glycogen; astrocytes produce lactate to supplement glucose in neurones when demand is high/glucose is low (5-10min supply)
What are the functions of oligodendrocytes?
Insulate (myelinate axons in the CNS)
What are the functions of microglia?
Immunocompetent cells
- recognise foreign material (activation)
- phagocytose debris/foreign material
What are the functions of the blood-brain barrier? How is it formed?
- limits diffusion of substances from the blood to the ECF of the brain
- maintains the correct environment for neurones e.g. variations in [K+], amino acids (can act as neurotransmitters), hormones
Brain capillaries:
- tight junctions between endothelial cells (prevent diffusion of small molecules)
- basement membrane surrounding capillary
- end feet of astrocyte processes (also stimulate formation of tight junctions)
What are the features of the immune system of the CNS?
Immune privileged
- does not undergo rapid rejection of allografts
- rigid skull will not tolerate volume expansion, therefore too much inflammation will be harmful
- microglia act as antigen-presenting cells
- T-cells can enter but the CNS inhibits the initiation of the pro-inflammatory T-cell response (limiting inflammation)
What are the different classes of neurotransmitters in the CNS?
Amino acids =
- glutamate (excitatory)
- GABA (inhibitory - brain)
- glycine (inhibitory - brainstem & spinal cord)
Biogenic amines (neuromodulators confined to specific pathways) =
- acetylcholine
- noradrenaline
- dopamine
- serotonin (5-HT)
- histamine
Peptides =
- somatostatin
- cholecystokinin
- neuropeptide Y
What are some of the important glutamate receptors present in glutamatergic synapses?
AMPA receptors (fast) - Na+/K+ - mediate the initial fast depolarisation
NMDA receptors (slow) - Na+/K+ & Ca2+
- permeable to Ca2+ —> role in learning & memory
- need glutamate to bind (glycine is a co-agonist) AND the cell to be depolarised (Mg2+ plugs the channel unless depolarised)
- activation up-regulates AMPA receptors
note: infarcted brain tissue releases Ca2+ —> increase Ca2+ entry into surrounding cells —> increased excitability
note: strong, high freq. stimulation of NMDA receptors causes long term potentiation (enhanced synaptic response)
How do barbiturates & benzodiazepines affect neurotransmitters in the CNS?
Bind to GABA receptors —> enhances response to GABA binding —> inhibitory post-synaptic potential (IPSPs) —> reduced firing
Outline the cholinergic pathways in the CNS. What functions do they perform? How is it involved in disease?
Hippocampus —> septohippocampal pathway —> septum
Nucleus basalis (frontal lobe —> extends through cortex)
Striatal interneurones
Thalamus
Functions:
- arousal
- learning & memory
- motor control
Degeneration of cholinergic neurones in nucleus basalis associated with Alzheimer’s disease (cholinesterase inhibitors use to alleviate symptoms)
Outline the dopaminergic pathways in the CNS. What functions do they perform? How is it involved in disease?
Hippocampus & amygdala —> mesolimbic pathway —> pituitary gland & hypothalamus (tubero-hypophyseal pathway) —> mesocortical pathway
Substantia nigra —> nigrostriatal pathway —> corpus striatum
Functions:
- mesolimbic pathway = mood, arousal, reward, emotion
- mesocortical pathway = mood, arousal, reward, emotion
- nigrostriatal pathway = motor control
Parkinson’s disease associated with loss of dopaminergic neurones in nigrostriatal pathway (treated with levodopa —> converted to dopamine by DOPA decarboxylase)
Schizophrenia may be caused by release of too much dopamine (as amphetamines release dopamine & noradrenaline and produce schizophrenic-like behaviour)
(anti-psychotic drugs are antagonists at dopamine D2 receptors)
Outline the noradrenergic pathways in the CNS. What functions do they perform? How is it involved in disease?
Amygdala —> hippocampus —> extends through cortex & cerebellum
Reticular formation —> travels down spinal cord
Thalamus
Diffuse release of noradrenaline throughout cortex, hypothalamus, amygdala, & cerebellum
Cell bodies of neurones containing noradrenaline in pons & medulla
Most noradrenaline in the brain come from a group of neurones in the locus ceruleus (brainstem)
- inactivated during sleep
- activity increases during behavioral arousal (relationship between mood and state of arousal)
Amphetamines increase the release of noradrenaline & dopamine —> increase wakefulness
Depression may be associated with noradrenaline deficiency
Outline the serotonergic pathways in the CNS. What functions do they perform? How is it involved in disease?
Similar distribution to noradrenergic neurones:
Amygdala & hippocampus —> hypothalamus & thalamus —> corpus striatum —> extends throughout cortex & cerebellum
Functions:
- sleep
- wakefulness
- mood
Depression and anxiety disorders treated with serotonin selective re-uptake inhibitors (SSRIs)
Vomiting centre in brainstem
What are glia? What are the different types?
GLIA = connective tissue of the nervous system which support, nourish, and insulate neurones and remove waste
- astrocytes
- oligodendrocytes
- microglia
