Glial cells - Neurobiology and Clinical Aspects

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Anatomy and Physiological aspects of glial cells, Role in Health and Disease

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Glial cells - Neurobiology and Clinical Aspects

  1. 1. 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:
  2. 2. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  3. 3. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  4. 4. 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.
  5. 5. 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
  6. 6. 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)
  7. 7. 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.
  8. 8. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  9. 9. 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
  10. 10. Gliogenesis
  11. 11. Microgliogenesis
  12. 12. Central Neuroglia Astrocyte Oligodendrocyte Microglia
  13. 13. Astrocytes
  14. 14. Astrocytes
  15. 15. 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
  16. 16. Astrocytes
  17. 17. Astrocytes • Astrocytes contact virtually every cell component in brain • Other astrocytes (gap junctions) • Ependymal cells • Neurons (somas, processes, synapses) • Oligodendroglia • Capillary endothelial cells
  18. 18. 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.
  19. 19. 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.
  20. 20. 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.
  21. 21. 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
  22. 22. Astrocyte in association with a blood vessel
  23. 23. Oligodendrocytes
  24. 24. Myelination in CNS 12-27
  25. 25. Myelination in PNS • Myelination begins during fetal development, but proceeds most rapidly in infancy. 12-28
  26. 26. Oligodendrocyte
  27. 27. 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
  28. 28. Ultrastructure of white matter
  29. 29. Microglia The Brain’s Immune Cell
  30. 30. 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.
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. Figure 12.6 An Introduction to Neuroglia Figure 12.6
  35. 35. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  36. 36. Pathophysiology
  37. 37. 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
  38. 38. More reactive astrocytes (gliosis)
  39. 39. Road Map for the session • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  40. 40. Specific Conditions • Stroke
  41. 41. Specific Conditions • Stroke • Cerebral Oedema
  42. 42. Specific Conditions • Stroke • Cerebral Oedema • AD
  43. 43. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain
  44. 44. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy
  45. 45. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy • Glioma
  46. 46. Summary • Introduction • Classification – Types, Functions • Pathophysiology • Glial Cells in Disease
  47. 47. Specific Conditions • Stroke • Cerebral Oedema • AD • Neuropathic Pain • Epilepsy • Glioma

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