Glial Cells

Astrocytes

• Star shape

• Maintain blood brain barrier and overall environment for signalling

  • Rugulate iron, pH, NT (clears glutamate preventing excitotoxicity via ETS)

  • Regulate synaptogenesis, synaptic plasticity & metabolic stuff

• Stained using GFAP

• Two types

  • Protoplasmic astrocytes

  • Fibrous astrocytes

Protoplasmic Astrocytes

• In grey matter

• Envelope cell bodies and synapses.

• Most common

• Have organelles

• Are short thick and highly branched.

Fibrous Astrocytes

• In white matter

• Interact with the node of Ranvier and oligodendrocytes/myelinated axons.

• Long, unbranched with few organelles.

Role of Astrocytes in the Blood Brain Barrier

• BBB separates blood and CSF

• Astrocytes have endfeet that surround blood vessels

• This helps regulate nutrient uptake and waste clearance and mediates communication with vasculature.

• Secrete paracrine factor to promote BBB and formation of synapse

Astrocytes Promote Synapse Formation

• Secrete thrombospondins (TSP1/2 for excitatory synapses) that promote CNS synaptogenesis

• TSP are a family of 5 extracellular matrix proteins

• TSPs induce the formation of synapses by bind to a voltage gated calcium channel alpha 2 delta 1

• Gabapentin (anticonvulsant drug for epilepsy) inhibits excitatory synapse formation by stopping TSP from binding to receptors blocking TSP induced synaptogenesis.

Tripartite Synapses

• Presynaptic membrane, post synaptic membrane and glial cell (usually astrocyte)

• Active role of astrocytes in regulating synaptic function

• Bi-directional communication between astrocytes and neurons.

Astrogliosis

• When astrocytes react to insults or inflammation

• Astrocytes become thicker and more branched and secrete anti inflammatory molecules (cytokines)

• Mild astrogliosis is associated with trauma and when initial trigger is resolved potential for resolution.

• Servere astrogliosis is associated with focal lesions, infections and neurodegenerative disorders.

  • There is astrocyte proliferation and formation of glial scars as a barrier to protect the CNS post injury.

  • This can prevent recovery and produce permanent scarring preventing recovery.

Microglia

• Clear debris and main life of defence when BBB is broken.

• IBA1 is a microglia/macrophage specific calcium binding protein to mark microglia.

• Small cell bodies with highly mobile cell processes

• Derived from bone marrow from hematopoietic stem cells

• They present antigens and perform phagocytosis

• They are mobile and will move towards chemoattractant cues released by dying cells

• Material is tethered and engulfed in a phagosome

• Phagosome matures and fuses with lysosomes and material is degraded

  

Types of Microglial

• Amoeboid Microglia

  • Rounded

  • No phagocytosis or immune function

  • Prevalent during development and reshaping

• Ramified (resting) microglia

  • Highly branched

  • Multiple processes and small body

  • No phagocytosis or immune function

  • Maintain immunologically stable environmentment

  • Present in adulthood

• Activated microglia

  • Thicker shorter branches

  • Fully phagocytotic

  • Secrete pro-inflammatory mediators (Nitric oxide NO and tumour necrosis factor TNF) and neurotoxic

  • Antigen presenting

Oligodendrocytes

• Form myelin in the CNS

• Can myelinate many (30) neurons

Schwann Cells

• Form myelin in the PNS

Composition of Myelin

CNS	PNS
High in myelin basic protein (MBP) cytoplasmic High in proteolipid protein (PLP) hydrophobic transmembrane protein that makes the myelin more compact	High in protein 0 (P0) transmembrane protein with immunoglobulin domains (antibodies) P0 associated with P0 in another layer and zips the extracellular membrane to make it more compact Peripheral myelin protein 22 (PMP22) hydrophobic transmembrane protein

Demyelinating diseases

• In the CNS MBP and PLP can act as autoantigens and cause multiple sclerosis

• In the PNS PO and PMP22 act as autoantigens (Guillean Barrs syndrome)