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    Neuroglia - PDF (Ingles)

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    Médecin Adrian TG
    The document discusses the cellular organization of the nervous system known as neuroglia. There are 5 main types of neuroglia that support and protect neurons: astrocytes, ependymal cells, oligodendrocytes, Schwann cells, and microglia. Astrocytes perform many roles like maintaining the blood-brain barrier, providing nutrients and signaling to neurons, and regulating synapses. Oligodendrocytes and Schwann cells form myelin sheaths around axons to allow for faster signal conduction. Microglia act as the immune cells of the central nervous system. Neuroglia are essential for proper functioning and maintenance of the nervous system.

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    © All Rights Reserved
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    Neuroglia - PDF (Ingles)

    Uploaded by

    Médecin Adrian TG
    176 views29 pages
    The document discusses the cellular organization of the nervous system known as neuroglia. There are 5 main types of neuroglia that support and protect neurons: astrocytes, ependymal cells, oligodendrocytes, Schwann cells, and microglia. Astrocytes perform many roles like maintaining the blood-brain barrier, providing nutrients and signaling to neurons, and regulating synapses. Oligodendrocytes and Schwann cells form myelin sheaths around axons to allow for faster signal conduction. Microglia act as the immune cells of the central nervous system. Neuroglia are essential for proper functioning and maintenance of the nervous system.

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    Neuroglia.pdf (Ingles)

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    The document discusses the cellular organization of the nervous system known as neuroglia. There are 5 main types of neuroglia that support and protect neurons: astrocytes, ependymal cells, oligodendrocytes, Schwann cells, and microglia. Astrocytes perform many roles like maintaining the blood-brain barrier, providing nutrients and signaling to neurons, and regulating synapses. Oligodendrocytes and Schwann cells form myelin sheaths around axons to allow for faster signal conduction. Microglia act as the immune cells of the central nervous system. Neuroglia are essential for proper functioning and maintenance of the nervous system.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    176 views29 pages

    Neuroglia - PDF (Ingles)

    Uploaded by

    Médecin Adrian TG
    The document discusses the cellular organization of the nervous system known as neuroglia. There are 5 main types of neuroglia that support and protect neurons: astrocytes, ependymal cells, oligodendrocytes, Schwann cells, and microglia. Astrocytes perform many roles like maintaining the blood-brain barrier, providing nutrients and signaling to neurons, and regulating synapses. Oligodendrocytes and Schwann cells form myelin sheaths around axons to allow for faster signal conduction. Microglia act as the immune cells of the central nervous system. Neuroglia are essential for proper functioning and maintenance of the nervous system.

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    © All Rights Reserved
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    of 29

    Lesson (1)

    The cellular organization


    of the nervous system
    (neuroglia)

    The neuroglia: structure and functions


    There is a debate on their actual number (formerly 10 times):
    now 2-3 times the number of the neurons

    5 main types:
    -Astrocytes
    MACROGLIA -Ependimal cells
    -Oligodendrocytes
    -Schwann cells
    -Microglia
    Functions:
    -Filter (Blood-Brain Barrier)
    -Physical support
    -Protection (sequestration of ion or neurotransmitters in excess;
    resident immune system)
    -Trophic and metabolic support
    -Signal transduction (transcytosis, myelin formation)
    -Regeneration and degeneration/scar formation (neural stem cells)

    What are glia?


    Neuroglia=nerve glue (Virchow, 1859)
    Glia as cells: S. Ramon y Cajal, P. del Rio-Hortega, 1900-1920

    A spatial view of neuroglial Cells of CNS

    THE NEUROGLIA:
    some FUNCTIONs

    Astrocytes & Ependimal cells: Blood brain


    barrier, support, trophic, signalling, support, homeostasis

    Oligodendrocytes
    Support & myelin, signalling
    Schwann Cells
    Microglia: resident immune system

    Astrocyte/capillary
    interactions: foot process

    Two types of astrocytes


    -Protoplasmic (pedunculated) in the grey matter
    - fibrous in the white matter
    Pedunculated astrocytes

    Fibrous astrocyte in the cerebellum white matter

    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
    Trophic support of neurons (growth
    factors)
    Homeostasis of neuronal
    microenvironment
    Ionic
    Metabolic
    Neurotransmitter uptake
    Blood-Brain barrier: induction and
    maintenance
    Synaptogenesis and synaptic remodeling

    Astrocytes
    Astrocytes contact virtually every cell
    component in brain
    Other astrocytes (gap junctions)
    Ependymal cells
    Neurons (somas, processes, synapses)
    Oligodendroglia
    Capillary endothelial cells

    Astrocytes
    Trophic function:
    produce growth factors/neurotrophic factors (NGF,
    BDNF, GDNF, CNTF, FGFs), especially in
    development and regenerative responses to injury
    Buffer extracellular space to maintain
    homeostasis for neuronal function:
    K+ spatial buffering
    Protect neurons from excitoxicity: active glutamate
    uptake/conversion to glutamine (cycled back to
    neurons)

    Astrocytes communicate with each other,


    other glia, and neurons via intercellular calcium waves
    mediated by GAPGAP-junctions and extracellular signals

    Calcium Waves in Retinal Glial Cells


    Eric A. Newman and Kathleen R. Zahs
    Science 1997 February 7; 275: 844-847.

    Glia work in unsuspected ways: synaptic


    depression after glia contacts synapses

    AChBP as a
    nAChR decoy

    Nature 411, 261 - 268 (2001)

    How did they figure this out?


    (or, what does it take to get a paper in Nature?)

    Observation:
    Cultured neurons formed Ach synapses
    When glia were allowed to contact synapses, synaptic
    depression was observed

    Question:
    How do the glia sense and respond to the Ach to modulate
    transmission ?

    Finding:
    It senses Ach by AchBP (identified by Bungarotoxin
    purification scheme, partial AA sequence)

    Response:
    Glia have nAChR, which senses increased Ach and induces
    release of AChBP from glia into the cleft, suppressing
    transmission (negative feedback).

    Who are the stem cells of the adult brain?


    astrocytes vs. ependymal cells
    The subventricular zone

    Ependymal cells
    June 15, 1999

    Astrocytes

    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 in disease: gliosis

    Astrocytosis/gliosis
    = response of astrocytes
    to many forms of injury:
    trauma, inflammation, MS,
    infection,
    neurodegeneration
    MS plaque: GFAP

    Astrocytes-gliosis
    Classical description of gliosis is:
    hypertrophy,
    +/- proliferation,
    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

    Reality: there must be many distinct forms of


    astrocyte activation; hundreds or thousands of
    distinct changes in gene expression

    More reactive astrocytes


    (gliosis)

    BBB=endothelial tight
    junctions

    Basment membrane

    Endothelial

    10

    Ependymal cells
    Line ventricles of brain and spinal cord canal
    Ciliated, columnar epithelium, with cilia and
    adherens junctions; but express glial markers
    May extend cytoplasmic processes into brain
    parenchyma
    Recent controversy as to whether Ependymal
    cells (versus subependymal astrocytes) are
    adult neural stem cells

    11

    Ependymal cells

    Chroiod plexus

    12

    Oligodendroglia (CNS)

    Oligodendroglia (CNS)
    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

    13

    Ultrastructure of white matter

    Oligodendroglia
    1 glial cell forms myelin around many axons

    14

    Schwann Cell (PNS)

    Schwann Cell

    Theodore Schwann (19th cent. German anatomist; a key founder of


    cell theory)
    Each Schwann cell wraps a portion of a single peripheral axon

    15

    Myelinated perypheral axons

    Myelin 1
    Myelin acts as an insulator for vertebrate
    nerve cells
    Cellular structure - myelin is composed of
    alternating layers of protein and lipid (20%
    protein and 80 % lipid (looks white)

    Very little cytoplasm between layers


    Myelin represents a major vertebrate feature
    Not a major factor in invertebrates nervous systems
    Major advantages
    faster conduction (10x)
    smaller sized neurons (10x)

    16

    Myelin 2
    Oligodendrocytes in CNS and Schwann cells in PNS
    Oligodendrocytes in CNS myelinate several fibers
    myelination spirals inward with new layers pushed under the older
    ones

    In CNS - no neurilemma or endoneurium


    In PNS, hundreds of layers wrap axon
    the outermost coil is schwann cell (neurilemma)
    covered by basal lamina and endoneurium

    Gaps between myelin segments = nodes of Ranvier


    Initial segment (area before 1st schwann cell) and
    axon hillock form trigger zone where signals begin

    Myelin Sheath

    Note: Node of Ranvier between Schwann cells

    17

    Myelination in PNS

    Myelination begins during fetal development, but


    proceeds most rapidly in infancy.

    Unmyelinated Axons of PNS

    Schwann cells hold small nerve fibers in


    grooves on their surface with only one
    membrane wrapping

    18

    Myelination in CNS

    Speed of Nerve Signal


    Diameter of fiber and presence of myelin
    large fibers have more surface area for signals

    Speeds
    small, unmyelinated fibers = 0.5 - 2.0 m/sec
    small, myelinated fibers = 3 - 15.0 m/sec
    large, myelinated fibers = up to 120 m/sec

    Functions
    slow signals supply the stomach and dilate pupil
    fast signals supply skeletal muscles and transport sensory
    signals for vision and balance

    19

    Impulse Conduction - Unmyelinated Fibers

    Saltatory Conduction - Myelinated Fibers


    Voltage-gated channels needed for APs
    fewer than 25 per m2 in myelin-covered regions
    up to 12,000 per m2 in nodes of Ranvier

    Fast Na+ diffusion occurs between nodes

    20

    Peripheral Nerve (Fascicle)

    Perineurium

    Endoneurium

    Myelinated axons

    Peripheral nerve

    21

    Neuropathological note
    Tumors of the nervous system are largely
    Glial tumors:
    Peripheral: Schwannoma, Neurofibroma
    Central:
    astrocytomas (includes benign pilocytic astrocytic
    and most common and most malignant:
    glioblastoma multiforme)
    Oligodendrogliomas
    ependymomas

    Multiple Sclerosis is an autoimmune


    attack on white matter

    22

    Major proteins found in Myelin


    P0 (protein zero) intraperiod line formation
    a glycoprotein only in myelin-forming Schwann cells (50%)
    similar to CAMs, but bifunctional (in PNS)

    proteolipid protein (PLP) intraperiod line formation


    only in Oligodendrocytes (50%) (in CNS)

    myelin basic protein (MBP)


    expressed in both, involved in compaction
    very antigenic, can be used to induce experimental multiple
    scelerosis, (T-lymphocyte inv. of CNS and PNS
    shiverer in mice

    NCAM
    Cellular adhesion

    How these proteins work together

    23

    Schwann Cells and Peripheral


    Neuropathies
    Schwann cells also perform trophic functions
    (NGF production in regeneration).
    Myelin proteins
    Schwann cells (PNS): P0, PMP22
    CMT1A=duplication of PMP22
    HNPP=deletion of PMP22 (surprisingly, deletion causes
    milder phenotype than CMT1A(duplication)

    Radial glia
    Embryonic scaffold throughout CNS
    Guides for radial migration of neurons
    Produce matrix and adhesion proteins

    24

    Radial glia
    Adult: radial glia persist in cerebellum
    (Bergmann glia) and in retina (Muller cells)

    GFAP

    Gliogenesis
    Note the absence
    of microglia from
    this family tree!

    25

    Microglia: OX-42

    26

    Microglia (as opposed to


    Macroglia=astrocytes, oligos)
    Most like tissue macrophages elsewhere in body; not
    of neuroectodermal origin, like all macroglia
    Chief mediators of immune responses in brain
    CNS is not completely isolated from immune
    reactions
    Microglia derive from marrow monocyte lineage
    Have phenotypic markers similar to tissue
    macrophages:
    CD68, HAM-56, IL-1alpha,beta, class II MHC, OX-42

    Microglia
    Most roles for microglia in context of CNS pathology;
    little known yet about normal functions. Examples of
    possible normal function are developmental:
    phagocytosis of apoptotic neurons; secretion of factors
    Activated microglia can produce and secrete cytokines
    capable of activating astrocytes: e.g. IL-1; some think
    microglia are the primary sensors of CNS damage.
    Some say that they have no function in the healthy
    adult brain: They dont form a network with intercellular
    junctions, as do neurons and astrocytes
    LIKE BODYGUARDS: THEY JUST SIT THERE WAITING FOR
    AN INSULT

    27

    Microgliogenesis

    How do we know this is true?

    Microglial activation

    28

    Microglia

    Blood-brain Barrier

    29

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