Reviewed
distinction between neurons and glial cells
neurones = electrically excitable - can generate and propogate action
potentials (APs), can’t survive without glia
glia = only have low density voltage gated channels so not excitable/no
APs, homeostatic cells of nervous system (not neurones/vascular) -
preservers and killers, ratio varies by region eg. cerebellum mostly
neurones but basal ganglia mostly glia
greater changes seen evolutionarily in astrocytes than neurones = with
species development see inc in glia:neurone ratio (eg. drosophilia 1:4,
human 9:10) and inc size/complexity of glia
human protoplasmic astro are only 2.5x larger linearly but have a 17x
greater volume, 10x more processes and 100x connections vs rat
main types of glia and lineages
CNS - macroglia
lineage = ectodermal, neural origin
pluripotent neural progenitor stem cells from neuroepithelium of neural
tube > multiply/divide symmetrically > divide asymmetrically = neuroblasts
and radial glia (soma lies in ventricular zone, processes extend into pia,
unique markers) > neuroblasts into neurones + RG into intermediate
progenitors (neuronal, astroglial, oligodendroglial, ependymal) >
interkinetic nuclear migration to pia then differentiate/mature
end of embryonic development: RG transform into adult neural stem cells
(eg. parenchymal astrocytes/RGLC/muller cells in retina) in subventricular
zone of lateral ventricles and subgranular zone of dentate gyrus >
continue to generate neurones/astrocyes/oligodendrocytes = adult
neurogenesis
Summary 1
, Number of glial increases 6-8x in first 3 weeks of postnatal life, while
neurogenesis of neurones mainly complete by birth
1. astroglia
lineage
derived from radial glia, astrocyte progenitors, oligodendrocyte
precursors, or symmetric division of astrocytes postnatally
foetal differentiation governed by GFAP/S100B genes +
JAKSTAT/notch/BMP-SMAD signalling
morphology
protoplasmic (stellate, branching processes, grey) or fibrous (white, non
branched processes), also interlaminar and varicose projection types in
primates
processes = plastic, motile lamellipodia/filopodia
endfeet of processes contact: synapses, capillaries, multiple dendrites,
nodes of ranvier, pia mater (glia limitans)
marker = glial fibrillary acidic protein GFAP - cytoskeletal, structure
support
organisation - reach of each astrocyte’s processes forms non overlapping
domains of distinct volume in the grey matter
properties
high resting K+ conductance, -90mV resting potential > useful for
buffering
Summary 2
, form functional synctium connected by gap junctions
respond to neurotransmitter (NT) signalling via Ca wave: glutamate binds
mGluR > IP3 generated > Ca released from ER > spreads through rest of
cell > either: IP3 moves via gap junction to trigger Ca wave in next in
syncytium OR Ca triggers extracellular ATP release which binds receptor
on next to trigger internal IP3 and continue chain
functions
1. CNS development
adult neurogenesis: stem cells (express nestin protein marker) found in
subgranular hippocampus and subventricular zone of olfactory bulb
also synaptogenesis (secretion of eg. cholesterol), synaptic
pruning/plasticity, migration
2. structure
define brain architecture, deliniate glia limitans
form neurovascular unit = cerebral capillary + endothelia + basement
membrane + astros + oligo + pericyte + neurones + microglia
3. barrier maintenance
endfeet form interface with blood capillaries to regulate permeation across
blood brain and blood CSF barriers
Summary 3
, support capillary endothelia: secrete trophic factors eg. GDNF to
strengthen tight junctions (prevent movement) and display polarised
expression of ion channels/transporters eg. LRP1 to selectively allow BBB
transport
4. homeostasis
spatial K+ buffering - local uptake via inwardly rectifying K4.1 channels
(also Na/K/ATP pump or Na/K/Cl co transporters) > K+ redistributed via
gap junctions across syncytium to prevent hyperexcitability near neurone
from frequent APs
pH - release H+ via MCT1, remove H+ via glutamate transporters
chemoception - sense CO/pH/Na changes
water - AQP4 aquaporin channels anchored by dystrophin/a-syntrophin
complex in perisynaptic endfeet membrane alongside K4.1/glu channels:
neuronal activity releases K+/glu which are uptaken by astro > water
follows osmotically (swelling of perisynaptic endfeet) > water redistributed
through synctium > water released via AQP4 on perivascular endfeet into
capillary > swelling decreased
Summary 4