glial cells - neurobiology and clinical aspects
DESCRIPTION
Anatomy and Physiological aspects of glial cells, Role in Health and DiseaseTRANSCRIPT
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.
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
