Download Radial glia

Neurobiology
Cells of the nervous system
Anthony Heape
2010
1
Cells of the nervous system
Neuroglia (or glial cells): part 1
The non-excitable cells of the nervous system that
provide support to neuronal survival and function
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Cells of the nervous system
Neurons
Neuroglia
 Functional classification
 Sensory or afferent: Action
potentials toward CNS
 Motor or efferent: Action
potentials away from CNS
 Interneurons or association
neurons: Within CNS from one
neuron to another
 Radial glia (embryonic)
 Structural classification
 Multipolar
 Bipolar
 (pseudo-) unipolar
 Schwann cells
Polarity is defined as the number of a neuron’s own
processes (extensions) that are directly associated with
the cell body (soma)
 Astrocytes
 Ependymal Cells
 Microglia
 Oligodendrocytes
 Satellite cells
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Neuroglia
CNS


Astrocytes
Regulate extracellular
brain fluid composition
Promote tight junctions to
form blood-brain barrier
Ependymal Cells
Line brain ventricles and
spinal cord central canal
Help form choroid
plexuses that secrete CSF

Microglia
Specialized macrophages

Oligodendrocytes
Form multiple myelin
sheaths around one or
more axons
PNS
Satellite cells
Surround neuron cell bodies in ganglia,
provide support and nutrients
Schwann cells
Wrap around one portion of only one
axon to form a single myelin sheath
Embryonic (?)
Radial glia
Neuroglia are about 10-fold more
abundant than neurons in the CNS
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Neuroglia
Non-myelinating glial cells of the CNS
Radial glia
Astrocytes
Microglial cells
Ependymal cells
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Cells derived
from the
neural tube
Central canal
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Radial
glia
Before
Now
 Present during embryonic
development.
 Provide a supporting scaffold
throughout CNS.
 Serve as guides for radial
migration of neurons.
 Produce extracellular matrix and
adhesion proteins.
 In the adult, radial glia (some now
consider these to be types of
astrocytes) appear to persist only
in the cerebellum, as Bergmann
glia, and in retina, as Müller cells.
•
Radial glia represent the main
population of neural progenitors in
many regions of the CNS,
•
The progeny of radial glia includes
all the main lineages of the CNS:





neurons,
astrocytes,
oligodendrocytes,
ependymocytes
adult neural stem cells
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Cells derived
from the
neural tube
Central canal
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Neurulation
Neural crest
Neural crest
Neural tube
notocord
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Cells of the
neural tube
External (basal) surface
S phase
G2 phase
Interkinetic nuclear migration
G1 phase
Mitosis
Ventricular (apical) surface
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Neuroepithelial
to radial glia
transition
• Neuroepithelial cells (NEP)
progressively convert to radial glia.
• Radial glia elongate following the
thickening of the neural tube wall.
• Basal progenitors are generated by:
 NEP at early stages,
 radial glia at later stages,
• Basal progenitors accumulate in the
SVZ.
• Neurons are generated by:
 basal progenitors at early
stages
 Radial glia and basal
progenitors at later stages.
Basal progenitor (BP)
Early stage neuron
Late stage neuron from BP
Late stage neuron
from RG
Radial glia (RG)
(Apical surface)
CP = cortical plate; SVZ = subventricular zone; VZ = ventricular zone
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Radial glia
Distinguishing
properties
NE = Neuroepithelial cells
RG = Radial glia
BP = Basal progenitors
 First wave of NE differentiation produces BPs,
which produce neurons
 Second wave of NE differentiation produces RGs,
which produce neurons, then CNS glial cells
Basal progenitor (BP)
Early stage neuron
Late stage neuron from BP
Late stage neuron
from RG
Radial glia (RG)
(Apical surface)
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Radial glia
progeny
Radial glia are neural cell precursors, not end-products as previously believed
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More about radial glia
Goldman S. (2003) Glia as neural
progenitor cells. Trends Neurosci..
26:590-596
Pinto L. & Götz M. (2007) Radial glia cell
heterogeneity – The source of diverse
progeny in the CNS. Prog. Neurobiol.
83:2-23
Malatesta P., Appolloni I. & Calzolari F.
(2008) Radial glia and neural stem
cells. Cell Tissue Res. 331:165-178
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Astrocytes
Most numerous cell type in brain.
Constitute ~30-50% of brain volume
Responsible for the the
regulation and optimization of
the functional environment of
CNS neurons
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Astrocytes
Astrocytes often communicate with each other,
other glia, and neurons via intercellular calcium
waves
Astrocytes contact and communicate
with almost every cell type in the CNS
 Neurons (somas, dendrites, axons at
nodes of Ranvier, synapses)
 Capillary endothelial cells (tight
junctions, forming blood-brain barrier)
 Oligodendroglia (soma and myelin
sheaths)
 Ependymal cells
 Other astrocytes (via gap junctions)
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Astrocytes
astroglia,
“star-cells”
FUNCTIONS
Development: Neurogenesis (adult), migration and differentiation
of neurons, and axon guidance
Synaptogenesis, synaptic remodeling and angiogenesis
Blood-Brain barrier: key roles in the formation and function of
the BBB (no structural role).
Trophic support of neurons (growth factors: NGF, BDNF, GDNF,
CNTF, FGF), especially in development and regenerative
responses to injury, source of extracellular matrix
components.
Homeostasis of neuronal microenvironment (K+ and metabolic,
and neurotransmitter uptake/recycling), regulate
extracellular brain fluid composition and contact and
communicate with almost every cell component in the
brain.
Signal transmission Transmission of neuronal signals, calcium
signalling
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Astrocytes
Astrocytes
participate in
neuronal signalling
And in the
formation of
the blood-brain
barrier
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The BloodBrain Barrier
(BBB)
•
The BBB is a cellular structure composed of
closely interconnected endothelial cells (tight
junctions) that form the blood vessel walls,
surrounded by a continuous sheath of
astrocytes, which regulate the BBB function.
•
The BBB restricts the passage of various
chemical substances and microscopic
organisms (e.g. bacteria) between the
bloodstream and the CNS neural tissue, while
still allowing the passage of substances
essential to metabolic function (e.g. Oxygen,
Glucose, ...).
•
The BBB acts very effectively to protect the brain
from many common bacterial infections. Thus,
infections of the brain are very rare.
•
Viruses can easily pass through the BBB.
•
Antibodies cannot cross the BBB, so infections
of the brain which do occur are often very
serious and difficult to treat.
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Neuroglia
More about
astrocytes
Wang DD., & Bordey. (2008) The astrocyte
odyssey. Prog. Neurobiol. 86:342-367
Seth P. & Koul N. (2008) Astrocyte, the
star avatar: redefined. J. Biosci.
33:405-421
Fellin T. (2009) Communication between
neurons and astrocytes: relevance to
the modulation of synaptic and network
activity. J. Neurochem. 108:533-544
blood-brain barrier
Wolberg H., Noell S., Mack A., WolbergBuchholz K. & Fallier-Becker P. (2009)
Brain endothelial cells and the gliovascular complex. Cell Tissue Res.
335:75-96
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Ventricles, canals &
cerebrospinal fluid
(CSF)
CSF circulates from the choroid plexus
through the ventricles of the brain and the
central canal of the spinal cord, and fills
the subarachnoid space located between
the arachnoid mater and the pia mater.
Lumen
Of
Neural
tube
Frontal view
Lateral view
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Ependymal
cells
Ventricular
lumen
NORMAL FUNCTIONS
 Line brain ventricles and spinal cord
central canal
 Cilia circulate the cerebrospinal fluid
 Filtration barrier for brain molecules
and protection against harmful
substances.
 Help form choroid plexuses that
secrete CSF
cilia
Ventricular
lumen
Ependymal cells
Ciliated, columnar
epithelium, with
microvillae, adherens and
tight junctions; but express
glial markers (e.g. GFAP)
Choroid plexus
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Neuroglia
More about
Ependymal cells
Bruni JE. (1998) Ependymal development,
proliferation, and functions: a review.
Microsc. Res. Tech. 41:2-13
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Microglia
Microglial origin is controversial
Most believe that microglia are of
mesodermal origin, probably of the
bone marrow monocyte/macrophage
lineage, and do NOT originate from
the neuroepithelium like the other
glial cells.
These cells would enter the CNS from
the blood stream, before the
formation of the blood-brain barrier.
Resident tissue macrophages
of the CNS
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Microglia
FUNCTIONS
 Specialized immune cells that act as the macrophages of the CNS,
 phagocytose invading microorganisms and dead neurons
 Chief mediators of immune responses in brain
 primary sensors of CNS damage.
 Activated microglia can produce and secrete cytokines capable of
activating astrocytes: e.g. IL-1.
They do not form stable
cellular networks, as do
neurons and astrocytes
 Participate in cell survival, neural growth and regeneration
Derived from bone marrow
monocyte lineage, microglia are
the smallest and least abundant
glial cell type in brain.
Express phenotypic markers
similar to tissue macrophages:
CD68, HAM-56, IL1alpha,beta, class II MHC,
and OX-42
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Neuroglia
More about Microglial cells
Cuadros MA. & Navascués J. (1998) The Origin and
Differentiation of Microglial Cells During
Development. Progr. Neurobiol. 56:173-189.
Chan WY., S. Kohsaka S., Rezaie P.(2007) The
origin and cell lineage of microglia - New
concepts. B r a i n R e s. R e v. 5 3:3 4 4 –3 5 4.
Kim SU. & de Vellis J. (2005) Microglia in Health
and Disease. J. Neurosci. Res. 81:302–313.
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Non-myelinating glial
cells of the PNS
Satellite
cells
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Satellite
glial cells
Located in the sensory (dorsal root)
and sympathetic chain ganglia
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Satellite glial cells
Dorsal Root Ganglion
neuron cell body
axons
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Satellite
glial cells
• Satellite glial cells, like the ganglion neurons,
derive from the neural crest.
• Cultured embryonic satellite glial cells isolated
from rat DRGs can transform into astrocytes,
oligodendrocytes and Schwann cells
• The most selective phenotypic marker for Satellite
cells is Glutamine Synthase (converts Glu to Gln)
Immunocytochemistry
for GS in DRG
Note: astrocytes
also express GS
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Satellite
glial cells
Functions
Satellite cells provide support
and nutrients to neurons.
 Barrier function of the sheath: not absolute, but can contribute to
the control of neuronal extracellular environment by limiting the
rate of diffusion of substances across the sheath.
 Removal of neurotransmitters (e.g. glutamate and GABA) from the
neuronal extracellular space.
 Provision of nutrients (e.g. glutamine, malate, lactate) to neurons
 Regulation of extracellular ion composition (spatial buffering) (?)
 Removal of, or protection from, toxic substances (?)
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Neuroglia
More about Satellite Glial Cells
Hanani M. (2005) Satellite cells in sensory
ganglia: from form to function. Brain
Res. Rev. 48:457-476.
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PNS glial cells : where do they all come from ?
 Boundary cap cells
are localized at the
spinal cord surface at
the nerve root entry
and exit zones.
 Boundary cap cells
give rise to all
Schwann cells of the
dorsal root (between
the spinal cord and
the DRG) and a
subpopulation of
ventral root Schwann
cells and DRG
satellite glia, as well
as to nociceptive
(pain-sensing) neurons.
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Myelinating
Neuroglia
PNS
CNS

Oligodendrocytes
Form multiple myelin sheaths
around one or more axons
Schwann cells
Wrap around one portion of only one axon to
form a single myelin sheath

Radial glia

Astrocytes
Regulate extracellular brain
fluid composition
Promote tight junctions to
form blood-brain barrier
Satellite cells
Surround neuron cell bodies in ganglia, provide
support and nutrients

Ependymal Cells
Line brain ventricles and
spinal cord central canal
Help form choroid plexuses
that secrete CSF

CNS
PNS
Microglia
Specialized macrophages
34