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Neuroglia
•

•

Outnumber neurons by about
10 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)

Central Neuroglia
Astrocyte
protoplasmic astrocyte
fibrous astrocyte

Oligodendrocyte
perineuronal satellite cell
interfascicular cell

Microglia
Ependymal Cell

Peripheral Neuroglia
Schwann Cell
in peripheral nerve
and ganglion
Capsular (Satellite) Cell
in ganglion
Gliogenesis
Microgliogenesis
Central Neuroglia

Astrocyte

Oligodendrocyte

Microglia
Astrocytes
Astrocytes
Astrocytes (astroglia) “star-cells”
Most numerous cell type in brain
Constitute ~30-50% of brain volume

NORMAL FUNCTIONS
Developmental: Migrational and
Axon guidance of neurons
Homeostasis of neuronal
microenvironment
Ionic
Metabolic
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
The subventricular
zone

Ependymal cells

astrocytes
June 15, 1999
Brain 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
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.
Astrocytes control synapse formation

Control of Synapse Number by Glia
Erik M. Ullian, Stephanie K.
Sapperstein, Karen S. Christopherson,
and Ben A. Barres
Science 2001 January 26; 291: 657-661.
Astrocytes communicate with each other,
other glia, and neurons via intercellular
calcium waves

Calcium Waves in Retinal Glial
Cells
Eric A. Newman and Kathleen R. Zahs
Science 1997 February 7; 275: 844-847.
Astrocyte
Astrocyte
• Protoplasmic Astrocyte: Gray Matter
• Fibrous Astrocyte: White Matter

Cell Body
‘potato’ shape nucleus, scarse pale cytopasm

Processes
- GFAP (glial fibroacidic protein): intermediate filament
- Perivascular Feet (Foot Process, Vascular End-Feet)
surrounding blood vessels

Specialized Astrocytes
- Bergmann’s gial cell, Muller cell, pituicyte
Astrocyte in association with a blood vessel
Oligodendrocytes
Myelination in CNS

12-27
Myelination in PNS

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

12-28
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 Brain’s
Immune Cell
Microglia’s
Immune Response
* Resting microglia in normal brain,
called ramified or resting
* Normally not Phagocytic

* Under some pathological condition,
like trauma, stroke or Alzheimer’s;
neurodegeneration occurs.
* Microglia become activated and
engulf the apoptotic cell, and
changing it’s shape to ameboid.
Identifing Microglia
A specific histochemical marker (lectin Ricinus communis
agglutini-1) for normal human microglia
H. Mannoji, H. Yeager, & L.E. Becker
Hypothesis
Microglia in normal human
brain can be specifically
demonstrated using the
lectin RCA-1, as detected
with the avidin-biotin
peroxidase method
Microglia
Microglia
Cell Body
slender, indented, heterochromatic nucleus
dark cytopasm
- prominent secondary lysosome

Processes
short, highly branched

Macrophage (Mononuclear Phagocytic) System
Mesenchymal Origin - Blood Monocyte
Increased in Inflammation
Ependymal Cell
Ependymal Cell
Epithelial Cell
lining ventricular surface
cilia and microvilli on luminal surface
simple cuboidal cell with round nucleus

Tanicyte
basal process, numerous in 3rd ventricle
most ependymal cell has basal process
(Chung & Lee, 1988)

Choroid Plexus Epithelial Cells
ion 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
Glial cells - Neurobiology and Clinical Aspects

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Glial cells - Neurobiology and Clinical Aspects

  • 1.
  • 2. Neuroglia • • Outnumber neurons by about 10 to 1 (the guy on the right had an inordinate amount of them). 6 types of supporting cells – 4 are found in the CNS:
  • 3. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 4. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 5. 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.
  • 6. 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
  • 7. 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)
  • 8. 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.
  • 9. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 10. Neuroglia (Neuroglial Cells) Neuroglia (Neuroglial Cells) Central Neuroglia Astrocyte protoplasmic astrocyte fibrous astrocyte Oligodendrocyte perineuronal satellite cell interfascicular cell Microglia Ependymal Cell Peripheral Neuroglia Schwann Cell in peripheral nerve and ganglion Capsular (Satellite) Cell in ganglion
  • 16. Astrocytes (astroglia) “star-cells” Most numerous cell type in brain Constitute ~30-50% of brain volume NORMAL FUNCTIONS Developmental: Migrational and Axon guidance of neurons Homeostasis of neuronal microenvironment Ionic Metabolic Neurotransmitter uptake Blood-Brain barrier: induction and maintenance Trophic support of neurons (growth factors) Synaptogenesis and synaptic remodeling
  • 18. Astrocytes • Astrocytes contact virtually every cell component in brain • Other astrocytes (gap junctions) • Ependymal cells • Neurons (somas, processes, synapses) • Oligodendroglia • Capillary endothelial cells
  • 19. stem cells of the adult brain? astrocytes The subventricular zone Ependymal cells astrocytes June 15, 1999 Brain 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 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.
  • 20.
  • 21. Astrocytes control synapse formation Control of Synapse Number by Glia Erik M. Ullian, Stephanie K. Sapperstein, Karen S. Christopherson, and Ben A. Barres Science 2001 January 26; 291: 657-661.
  • 22. Astrocytes communicate with each other, other glia, and neurons via intercellular calcium waves Calcium Waves in Retinal Glial Cells Eric A. Newman and Kathleen R. Zahs Science 1997 February 7; 275: 844-847.
  • 23. Astrocyte Astrocyte • Protoplasmic Astrocyte: Gray Matter • Fibrous Astrocyte: White Matter Cell Body ‘potato’ shape nucleus, scarse pale cytopasm Processes - GFAP (glial fibroacidic protein): intermediate filament - Perivascular Feet (Foot Process, Vascular End-Feet) surrounding blood vessels Specialized Astrocytes - Bergmann’s gial cell, Muller cell, pituicyte
  • 24. Astrocyte in association with a blood vessel
  • 25.
  • 28. Myelination in PNS • Myelination begins during fetal development, but proceeds most rapidly in infancy. 12-28
  • 30. 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
  • 33. Microglia’s Immune Response * Resting microglia in normal brain, called ramified or resting * Normally not Phagocytic * Under some pathological condition, like trauma, stroke or Alzheimer’s; neurodegeneration occurs. * Microglia become activated and engulf the apoptotic cell, and changing it’s shape to ameboid.
  • 34. Identifing Microglia A specific histochemical marker (lectin Ricinus communis agglutini-1) for normal human microglia H. Mannoji, H. Yeager, & L.E. Becker Hypothesis Microglia in normal human brain can be specifically demonstrated using the lectin RCA-1, as detected with the avidin-biotin peroxidase method
  • 35. Microglia Microglia Cell Body slender, indented, heterochromatic nucleus dark cytopasm - prominent secondary lysosome Processes short, highly branched Macrophage (Mononuclear Phagocytic) System Mesenchymal Origin - Blood Monocyte Increased in Inflammation
  • 36. Ependymal Cell Ependymal Cell Epithelial Cell lining ventricular surface cilia and microvilli on luminal surface simple cuboidal cell with round nucleus Tanicyte basal process, numerous in 3rd ventricle most ependymal cell has basal process (Chung & Lee, 1988) Choroid Plexus Epithelial Cells ion transporting cell: numerous mitochondria
  • 37.
  • 38. Figure 12.6 An Introduction to Neuroglia Figure 12.6
  • 39. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 41.
  • 42. 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
  • 44.
  • 45.
  • 46.
  • 47.
  • 48.
  • 49. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 51.
  • 52.
  • 53.
  • 54.
  • 56.
  • 57. Specific Conditions • Stroke • Cerebral Oedema • AD
  • 58.
  • 59. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain
  • 60.
  • 61. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy
  • 62.
  • 63. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy • Glioma
  • 64.
  • 65.
  • 66. Summary • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  • 67. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy • Glioma