Glial cells - Neurobiology and Clinical Aspects

Neuroglia

• Outnumber neurons by about10 to 1 (the guy on the right had an inordinate amount of them).

• 6 types of supporting cells– 4 are found in the CNS:

Road Map for the session

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

Road Map for the session

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

The central nervous system consists of neurons and glial cells.  Neurons constitue about half the volume of the CNS and glial

cells make up the rest.  Glial cells provide support and protection for neurons.  They

are thus known as the "supporting cells" of the nervous system. 

Glia cells

•Although glia cells DO NOT carry nerve impulses (action potentials) they do have many important functions. In fact,

without glia, the neurons would not work properly!

Astrocytes, like most glial cells, were long considered essential for their role in supporting and maintaining

nerve tissue. But more and more evidence indicates that astrocytes may actually play a far more important role in

neural communication

The four main functions of glial cells are:

- to surround neurons and hold them in place - to supply nutrients and oxygen to neurons - to insulate one neuron from another - to destroy and remove the carcasses of dead neurons (clean up)

Function of glia cells

Some glia function primarily as physical support for neurons. Others regulate the internal environment of the brain, especially the fluid

surrounding neurons and their synapses, and provide nutrition to nerve cells.

Glia have important developmental roles, guiding migration of neurons in early development, and producing molecules that modify the growth

of axons and dendrites.

Recent findings in the hippocampus and cerebellum have indicated that glia are also active participants in synaptic transmission, regulating

clearance of neurotransmitter from the synaptic cleft, releasing factors such as ATP which modulate presynaptic function, and even releasing

neurotransmitters themselves.

Road Map for the session

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

Neuroglia (Neuroglial Cells)Neuroglia (Neuroglial Cells)Neuroglia (Neuroglial Cells)Neuroglia (Neuroglial Cells)

Central NeurogliaCentral Neuroglia AstrocyteAstrocyte protoplasmic astrocyteprotoplasmic astrocyte fibrous astrocytefibrous astrocyte

OligodendrocyteOligodendrocyte perineuronal satellite cellperineuronal satellite cell interfascicular cellinterfascicular cell

MicrogliaMicroglia Ependymal CellEpendymal Cell

Peripheral NeurogliaPeripheral Neuroglia Schwann CellSchwann Cell

in peripheral nervein peripheral nerve

and ganglionand ganglion

Capsular (Satellite) CellCapsular (Satellite) Cell

in ganglionin ganglion

Gliogenesis

Microgliogenesis

AstrocyteAstrocyte Oligodendrocyte Oligodendrocyte Microglia Microglia

Central NeurogliaCentral NeurogliaCentral NeurogliaCentral Neuroglia

Astrocytes

Astrocytes

Astrocytes (astroglia) “star-cells”Most numerous cell type in brain

Constitute ~30-50% of brain volume

NORMAL FUNCTIONSDevelopmental: Migrational and

Axon guidance of neurons

Homeostasis of neuronal microenvironment

IonicMetabolic

Neurotransmitter uptake

Blood-Brain barrier: induction and maintenance

Trophic support of neurons (growth factors)

Synaptogenesis and synaptic remodeling

Astrocytes

Astrocytes

Astrocytes contact virtually every cell component in brain

Other astrocytes (gap junctions) Ependymal cells Neurons (somas, processes, synapses) Oligodendroglia Capillary endothelial cells

stem cells of the adult brain?astrocytes

astrocytes

Ependymal cells

Johansson et al., "Identification of a neural stem cell in the adult mammalian central nervous system," Cell, 96:25-34, 1999. Doetsch et al., "Subventricular zone astrocytes are neural stem cells in the adult mammalian brain," Cell, 97:703-16, 1999.

June 15, 1999Brain Stem Cell Is Discovered,

Twice By NICHOLAS WADE

Dr Arturo Alvarez-Buylla and Dr Jonas Frisen report discovering site in brain of elusive neural stem cell, founding cell from which perhaps whole brain develops, but each scientist has a different site in

mind; Frisen contends that neural stem cells are cells that line

ventricles, while Buylla contends neural stem are the star-shaped

cells called astrocytes that lie one layer in from ventricle lining;

experts say their contradictory findings may yet be reconcilable

The subventricular zone

Control of Synapse Number by GliaErik M. Ullian, Stephanie K. Sapperstein, Karen S. Christopherson, and Ben A. BarresScience 2001 January 26; 291: 657-661.

Astrocytes control synapse formation

Calcium Waves in Retinal Glial Cells Eric A. Newman and Kathleen R. ZahsScience 1997 February 7; 275: 844-847.

Astrocytes communicate with each other, other glia, and neurons via intercellular

calcium waves

AstrocyteAstrocyteAstrocyteAstrocyte

• Protoplasmic Astrocyte: Gray Matter Protoplasmic Astrocyte: Gray Matter • Fibrous Astrocyte: White MatterFibrous Astrocyte: White Matter

Cell BodyCell Body ‘‘potato’ shape nucleus, scarse pale cytopasmpotato’ shape nucleus, scarse pale cytopasm

ProcessesProcesses - - GFAP GFAP (glial fibroacidic protein):(glial fibroacidic protein): intermediate filament intermediate filament

-- Perivascular Feet Perivascular Feet (Foot Process, Vascular End-Feet)(Foot Process, Vascular End-Feet) surrounding blood vesselssurrounding blood vessels

Specialized AstrocytesSpecialized Astrocytes

- Bergmann’s gial cell, Muller cell, pituicyte- Bergmann’s gial cell, Muller cell, pituicyte

Astrocyte in association with a blood vessel

Oligodendrocytes

12-27

Myelination in CNS

12-28

Myelination in PNS

• Myelination begins during fetal development, but proceeds most rapidly in infancy.

Oligodendrocyte

Oligodendroglia• “few-branch” glia

• Discovered by del Rio-Hortega, using metallic impregnation techniques in 1921

• one oligo myelinates many CNS axons

• CNS myelinators (white matter)

• Target of autoimmune attack in MS

• Specific oligodendrocyte myelin proteins: – PLP– DM20– MBP

Ultrastructure of white matter

Microglia

The BrainThe Brain’’s s Immune Immune

CellCell

MicrogliaMicroglia’’s s Immune ResponseImmune Response

* Resting microglia in normal brain,* Resting microglia in normal brain, called ramified or restingcalled ramified or resting

* Normally not Phagocytic* Normally not Phagocytic

* Under some pathological * Under some pathological condition,condition,

like trauma, stroke or like trauma, stroke or AlzheimerAlzheimer’’s; s;

neurodegeneration occurs.neurodegeneration occurs.

* Microglia become activated and * Microglia become activated and engulf the apoptotic cell, andengulf the apoptotic cell, and

changing itchanging it’’s shape to ameboid.s shape to ameboid.

Identifing MicrogliaIdentifing MicrogliaA specific histochemical marker (lectin A specific histochemical marker (lectin

Ricinus communis agglutini-1) for normal Ricinus communis agglutini-1) for normal human microgliahuman microglia

H. Mannoji, H. Yeager, & L.E. H. Mannoji, H. Yeager, & L.E. BeckerBecker

HypothesisHypothesis

Microglia in normal human brain can be

specifically demonstrated using the lectin RCA-1, as detected with the avidin-biotin peroxidase method

MicrogliaMicrogliaMicrogliaMicroglia

Cell BodyCell Body slender, indented, heterochromatic nucleusslender, indented, heterochromatic nucleus dark cytopasmdark cytopasm - prominent secondary lysosome- prominent secondary lysosome

ProcessesProcessesshort, highly branchedshort, highly branched

Macrophage (Mononuclear Phagocytic) SystemMacrophage (Mononuclear Phagocytic) SystemMesenchymal Origin - Blood MonocyteMesenchymal Origin - Blood MonocyteIncreased inIncreased in Inflammation Inflammation

Ependymal CellEpendymal CellEpendymal CellEpendymal Cell

Epithelial Cell Epithelial Cell lining ventricular surfacelining ventricular surface cilia and microvilli on luminal surfacecilia and microvilli on luminal surface simple cuboidal cell with round nucleussimple cuboidal cell with round nucleus

TanicyteTanicytebasal process, numerous in 3rd ventriclebasal process, numerous in 3rd ventriclemost ependymal cell has basal processmost ependymal cell has basal process (Chung & Lee, 1988)(Chung & Lee, 1988)

Choroid Plexus Epithelial CellsChoroid Plexus Epithelial Cellsion transporting cell: numerous mitochondriaion transporting cell: numerous mitochondria

Figure 12.6 An Introduction to Neuroglia

Figure 12.6

Road Map for the session

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

Pathophysiology

Astrocytes in Disease:Gliosis

Prominent expression of intermediate filaments: “Glial filaments”:

Glial Fibrillary Acidic Protein (discovered as a major component of Multiple Sclerosis White Matter Plaques;)

Also, vimentin, nestin

MS plaque: GFAP

More reactive astrocytes(gliosis)

Road Map for the session

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

Specific Conditions

• Stroke

Specific Conditions

• Stroke

• Cerebral Oedema

Specific Conditions

• Stroke

• Cerebral Oedema

• AD

Specific Conditions

• Stroke

• Cerebral Oedema

• AD

• Neuropathic Pain

Specific Conditions• Stroke

• Cerebral Oedema

• AD

• Neuropathic Pain

• Epilepsy

Specific Conditions• Stroke

• Cerebral Oedema

• AD

• Neuropathic Pain

• Epilepsy

• Glioma

Summary

• Introduction

• Classification – Types, Functions

• Pathophysiology

• Glial Cells in Disease

Specific Conditions• Stroke

• Cerebral Oedema

• AD

• Neuropathic Pain

• Epilepsy

• Glioma