NEUS 609 - Astrocytes

increases

The ratio of astrocytes to neurons for different species ___ with brain complexity and size.

fibrous

__ astrocytes are found mostly in white matter near axonal bundles.

2 million

1 astrocyte can be in contact with up to ___ synapses

Astrocytes’ Functions

• Regulate synapse formation, function, and elimination

• Induce formation of BBB and help with its structure

• Provide metabolic support, homeostasis, and control neuronal activity

• Contact node of Ranvier, oligodendrocytes, and microglia.

Astrocytes’ Markers

• GFAP (glial fibrillary acidic protein)

• Aldh1L1 (aldehyde dehydrogenase family 1 member L1)

• GLT1 (glutamate transporter 1)

• S100b (S100 calcium-binding protein B)

• Aquaporin 4 (water channel usually found near vasculature)

formation, maturation

Astrocytes induce synapse ___ and stimulate synapse ___

• very few synapses with no astrocyte present

• massive increase in synapse number when astrocytes generated

invading synaptic clefts, proteases

Excess synapses are eliminated by astrocytes’ processes ____ or by releasing ___ which degrade synapse stabilizing components.

• surviving synapses stabilized and stimulated by other signals

Thrombospondins

aka TSP-1/2

EXTRACELLULAR proteins that interact with integrins & are necessary for synaptic plasticity and functional recovery after a stroke.

• secreted by IMMATURE astrocytes

• interact with neuronal calcium channel subunit alpha2delta-1 to form synapses

immunoprecipitation

1- cell culture medium mixed with antibody against protein of interest

2- antibody binds to protein of interest

3- mixture incubated with beads that bind the antibody molecules

4- centrifugation separates beads-antibodies complexes from supernatant that is now free of protein in question.

Hevin

protein secreted by astrocytes to form synapses; induces bridging by interaction with neuroligin-1 and neurexin-1alpha

active, silent

Astrocytes secrete thrombospondins and hevin resulting in a presynaptically ___ but postsynaptically ___ due to the lack of AMPA receptors.

glypican

signal released by astrocytes which induce synapse FUNCTIONALITY by activating PTP receptors on presynaptic cell.

• leads to the release of NP1 (which is an AMPA clustering factor) in synaptic cleft increasing surface levels and clustering of GluA1 subunits of AMPA receptors on postsynaptic cell.

__ > PTP receptors > NP1 > GluA1 > AMPA

positive regulators

glypicans are ____ meaning that they INCREASE the number of postsynaptic AMPA receptors.

SPARC

__ is a negative regulator (decreases number of postsynaptic AMPA receptors) released by astrocytes.

• works by inhibiting the action of hevin

• also found in microglia

TGF-B

signal secreted by astrocytes to control EXCITATORY synapses formation in CNS

• also regulates formation of NMJ in PNS

BDNF

signal from astrocytes and microglia controlling excitatory synapse formation

• same function as TGF-B kind of

gamma-protocadherins

signal secreted by astrocytes to regulate EXCITATORY & INHIBITORY synapses through direct contact with neurons

phagocytosis

___ by astrocytes to eliminate synapses happens via MERKT and MEGF-10 receptors.

C1q

Astrocytes release TGF-B which induces expression of ___ in neurons

__ is a marker for weak/unwanted synapses and recruit microglia to phagocytose it.

tripartite

astrocytes are part of the ___ synapse and express NT receptors.

• following rise in calcium in astrocytes due to neuronally released NTs, substances like ATP are released to either inhibit or stimulate neuronal activity

Gliotransmitters controlling neuronal activity

• glutamate

• ATP

• GABA

• Nitric oxide (NO)

• D-serine (affects NMDA receptors and enhance neuronal acitvity)

NT concentration

Astrocytes regulate ___ in synaptic cleft

• Ex: too much glutamate leads to neurotoxicity so astrocytes take it out of cleft and recycle it

energy providers

astrocytes also are ___ by storing glucose as glycogen when blood sugar levels are high in CSF, so that they can give it to neurons as lactate when levels get low.

capillary

neurovascular unit

level at which astrocytes interact with the vasculature to induce BBB formation.

• end feet face blood vessel to form tight junctions where a lot of K+ and ATP channels are.

high, low

the ___ electrical resistance and __ permeability of the BBB is determined by astrocytes

glial fibrillary acidic protein

__ aka GFAP is necessary for BBB formation as KO had issues with BBB induction and formation

embryonic vascular endothelial, bidirectional

___ cells stimulate differentiation of immature astrocyte progenitors in a ___ manner: developing astrocytes also induce differentiation of astrocytes from progenitors.

occludin, claudin

levels of ___ and ___ (tight junction proteins) INCREASE after tight junctions created due to contact between astrocytes and endothelial cells

Shh, GDNF, Ang-1, RA, S1P

Mature astrocytes generate ____ to sustain BBB function by stimulating junctional protein expression.

glymphatic system

aka glial-lymphatic system

drains interstitial fluid (ISF)

Auquaporin4

___ channels in astrocytes facilitate the flow of CSF into the brain parenchyma & also facilitate flow of ISF into lymphatic system.

calcium increase

astrocytes can also regulate blood flow by controlling blood vessels dilation and constriction via intracellular ___

astrocytes blood flow regulation

1- neurally released glutamate activates astrocytes mGLURs which increase calcium levels

2- calcium activates PLA2 and increases levels of arachidonic acid (AA)

3- AA metabolized into vasoactive molecules like eicosanoids, PgE2 etc. causing VASODILATION

3- AA released into smooth muscle cells and metabolized into 20-HETE causing VASOCONSTRICTION.

pH, ion concentrations

astrocytes also regulate local ___ & ___ which help maintain homeostasis

• passive K+ transport

• Na+/K+ ATPase

• Na+/HCO3- cotransporter

• Na+/H+ antiporter (H+ outside)

interstitial K+

Astrocytes also control ___ concentration

• neuronally released K+ is taken up by astrocytes Kir4.1 (internally rectifying K+ channels)

• K+ redistributed in areas of LOW concentration via a network of gap junctions between neighboring astrocytes

glial maturation factor

glial factor affecting proliferation, survival, and differentiation of glia

aka GMF