Module IV - Lecture 2 - Glia Flashcards
To what extent do glia outnumber neurons and what role do they play and can they change function?
4:1, support role for neurons, and very dynamic and change function quickly
Where do most glial cells come from?
radial glial cells following a gliogenic switch
What are radial glial cells?
neural progenitor epithelial cells found in the embryonic neural tube and forebrain eventually become radial glial cells which can make more neurons and help neurons get to their final destination
What is the embryonic neural tube?
primitive spinal chord
What happens when a mitotic neuroepithelial cell divides?
one of the cells is a neuroepithelial cell and the sister cell goes on to become a neuron and this will continue to happen until the neurons pile up and then the neuroepithelial progenitor cells will become radial glial cells which can make more neurons ad help neurons get to their final destination
When do neuroepithelial progenitor cells become radial glial cells that can produce more neurons through cell division and help these neurons reach their final destination?
embryonic day 9
After making neurons what do radial glia cells undergo?
a gliogenic swicth and they become macroglia
What type of precursors can radial glial cells turn into and what do they give rise to?
-oligodendrocyte precursor cells that turn into oligodendrocytes which myelinate the CNS
-can also turn into astricyte through an unknown precursor
Where do CNS microglia come from?
stem cells in the embryonic yolk sac
What do hematopoietic stem cells in the yolk sac turn into?
blood cells including primitive macrophage which then migrate to the CNS and turn into microglia (same source as immune cells)
Where do glia of the PNS come from?
neural crest cells
What do neural crest cell first make?
sensory dorsal root ganglion neurons (project into the periperhy and transmit sensory information) which undergo a gliogenic swicth
AFter the gliogenic swicth what do neural crest cell make?
schwann cell precursors known as satellite glia
What do satellite glia do?
cushion and protect cell bodies in the PNS and serve astrocyte like roles
Where do schwann cell precursors migrate towards?
peripheral nerves and becomes myelinating shwann cells or remak cells which surround ,multiple axons and hold them close togetehr
What are remak cells?
come from schwann cell precursors and they can surround multiple acons and hold them close together
What is the most abunbdant cell type in the CNS and what three things to they do?
astrocytes
-trasnfer nutrients from blood vessles to neurons with activity
-can influence blood flow to regions to brain with more actuve neurons in response to NT release
-enhance the fidetlity of synaptic transmission (affect glutamatergic and inhibitory synaptogenesis by promoting or inhibiting it)
What do astrocyte glutamate transporters do?
take up glutamate to prevent too much activation of postsynaptic neuorns
What do astrocyte calcium permeable ampa receptors do?
they are activated by synaptic activity and result in astrocyte calcium waves that may signal enhanced high brain activity and are used to signal to blood vessels to increase blood flow to that area so there are a greater release of astrocyte mediated transfer of nutrients to active neurons
What are astrocytes connected by?
gap junctions whcih have alot of cytoplasmic continuity between them and and they can contact up to 1000 synapses in the region
How do astrocytes promote the function of glutamatergic synapses?
there are thrombospondins which are seceted by astrocytes and activate presynaptic calcium channels and the calcium signals help recruit presynaptic adhesion molecules presynaptic cell ashesion molecules like neurexins and they may also bind to postsynaptic neurligins directly to facilitate binding
What kinds of synapses to thromobospondins secreted by astrocytes make?
they make silent synapses that lack AMPARs - these synapses do have NMDA receptors though - act at both the presynaptic and postsynaptic cell
What is Hevin?
secreted by astrocytes and binds to presynaptic neurexins and and postsynaptic neurligins to promote their association and the development of excitatory synapses
What kind of synapses does hevin make?
silent synapses that lack AMPAR but have NMDA
What does SPARC do?
secreted by astrocytes and it may bind to and disrupt the ability of integrins to associate with the ecm proteins (lattice of proteins outside of synapses needed for proper positioning of synapses) and this results in an inhibition of synaptic development
What are ECM proteins?
form an extracellular latticework of proteins outside of neurons that synapses may rely on for proper positioning
How do astrocytes promote the maturation or unsilencing of glutamategric synapses?
they secrete glypican wehich binds to LAR receptors and promote the inertion of AMPA receptors in silent synapses
What is the LAR receptor glypican binds to?
it is a tyrosine phosphatse which is coupled to trio and causes actin poylemtization adn synapses get larger allowing for more ampa to be inserted into the synapse
If you culture astrocytes with neurons what happens to the number of exicitatory and inhibitory synapses you get? veruss if you culture neruons in the absence of astoryctes and what does this mean
-get more excitatory and inhibitory synapses if you culture the neurons with astrocytes and less if you do not culture them with astrocytes
-this means astrocytes are sufficient and necessary for synapse formation of inhibitory and excitatory synapses
When are synapses eliminated and what happens if you eliminate too many synapses?
-adolescence
-schizophrenia
What is responsible for synaptic pruning?
glia and microglia by squeezing between neurons and finding inactive synapses and phagocytozing them
How does glia or microglia synaptic pruning work?
astrocytes secrete this unknown factor onto neurons that causes them to express a C1 complex and they cleave C3 complement proteins that are floating in the extracellualr space to produce iC3b which binds to inactive synapses and very actuve synpases express proteins that prevent ic3b from binding to them microglia have cr3 receptors which binds to ic3b to identify weak synapses and phagocytize them
What is some proof that microglia phagocytosize presynaptuc terminals?
there are electron micrograph images of this
What do microglia do in terms of spines?
they can encapsulate dendritic spines and turn them back into filopodia
What also eats synapses and how?
astrocytes through the phagocytici recpetor Megf10 and MertK
What changes in response to injury?
microglia and astrocytes
How can astrocytes and microglia change their morphology for the good after injury?
can act as glutamate sponges with their GLUT transporters and take up glutamate released by dying neuron to prevent excitotoxicity and microglia can help break down bad or dying neurons
How can astrocytes and microglia change their morphology for the bad after injury?
over proliferation of glial cells can cause a glial scar that acts as barriers for axon regeneration and resstebalishment of axon connections
What myelinated axons in the cns and pns?
cns - oligodendrocytes promiscuous
pns - schwann cells
What else can oligodendrocytes and schwann cells for?
they may help nourish neurons
How can oligodendrocytes and schwann cells help nourish neurons?
myelin has MCT1 transporter which can shuttle lactate to neurons
What can myelin regulation be?
a form of CNS plasticity in learning - degree of meylinating or spacing of nodes of rnavier
What can schwann cells do post axon injury?
turn into pluripotent stem cells following axon injury to help break down damaged myelin and axons by releasing cytokine so macrophages can comes and chop up the axons and turn back into schwann cells that can form tunnel structures that can guid the new growth of an axon
