Download Neurocytology 2

Neuroanatomy: Neurocytology II- Neuroglia (Rafols)
INTRODUCTION:

Glia: form the interstitium between neurons
o Outnumber neurons by 10:1
o Comprise 50% of brain volume
o Retain ability to proliferate throughout life
o Selective markers reveal heterogeneity of form and involvement in disease processes
o Interact with neurons in their growth and survival
TYPES OF NEUROGLIA:

CNS:
Macroglia: derived from neuroectoderm
o Astrocyte: fibrous and protoplasmic
o Oligodendrocyte: most numerous
o Ependyma/tanycyte
Microglia: derived from mesoderm as blood vessels invade the developing brain; rarest type

PNS:
Schwann Cell: derived from neural crest
Satellite Cell: derived from neural crest
ASTROCYTES:

Fibrous: predominate in white matter (but also some in gray matter)
o Numerous long and smooth branches (star appearance)
o Processes terminate as cone-shaped expansions called end feet, which appose outer perimeter of blood
vessels

Protoplasmic: predominate in gray matter (but also some in white matter)
o Numerous short and irregular branches (fuzzy appearance)
o Processes terminate as cone-shaped expansions called end feet, which appose outer perimeter of blood
vessels

Continuous sheaths of glial end feet: isolate the neuronal compartment from potentially harmful agents in the
external and internal environments
o Inner glial limitans: under the ventricular lining ependyma
o Outer glial limitans: under the pia mater
o Pervascular glial sheath: around the perimeter of blood vessels

Microscopy:
Light: nucleus is round/indented; dispersed intranuclear chromatin forms small clumps on the inner aspect of
the nuclear envelope
EM: nucleus and cytoplasm are electron lucent; nuclear chromatin in small clumps on the inner aspect of nuclear
envelope; most prominent feature of the cytoplasm are the intermediate filaments containing GFAP

Functions:
Support:
o Radial glia in developing brain provide both support and a migration path for newly proliferated
neurons
o Structural integrity is provided by a complex cytoskeleton composed of macrofilaments (ie.
microtubules), intermediate filaments (ie. vimentin, glial filaments) and microfilaments (ie. actin)
Compartmentalization of Neuronal Functional Units:
o Processes isolate synapses and synaptic complexes (ie. synaptic glomerulus)
o Buffer K+ (acting as a K+ sink) from extracellular space immediately after depolarization; helps restore
transmembrane potential
BBB Formation and Maintenance:
o Tight junctions between adjacent endothelial cells of brain microvessels function as a barrier for
macromolecules in the blood
o However, adjacent glial end feet are coupled by gap junctions
o Glia together with endothelium form and maintain their intervening basal lamina and possibly the
endothelial tight junctions
Repair Processes After Injury or Disease:
o Astrocytes proliferate (hyperplasia) and/or increase in size (hypertrophy) in the formation of a scar
following injury or disease; this walls off the non-injured neuronal compartment
o Also participate in neuronophagia (phagocytosis of neuron parts; ie. axon terminals and dendritic
spines); part of synaptic remodeling associated with injury states or age-related synaptic plasticity
-
Secretion of Growth Factors:
o Insulin, IGF-1, NGF, BDNF and NT1-3 (neurotrophin 1,2,3) are all present in glia and play a role in
keeping neurons alive
o Different factors contribute selectively to viability of specific neuron phenotypes
o Lack of the above factors have been associated with a variety of disease processes
Regulation of Ionic Milieu:
o Previously mentioned K+ buffering (K+ sink)
o Aquaporins in endothelium and astroglia regulate water passage across BBB

Dysregulation of the channels may result in cerebral edema

Excessive accumulation of water leads to increased intracranial pressure (deleterious to
neurons)
 Vasogenic: in the extracellular compartment
 Cytotoxic: in the neural compartment
OLIGODENDROCYTES:

Basics:
Most numerous glial cell
Different forms exist in both gray and white matter
Function: to form and maintain central myelin or sheath of axons; distal most portion of an oligodendrocyte
process is continuous with the intermodal flap of myelin
o One oligodendrocyte can form as many as 50 internodal flaps of myelin
o Note: different from Schwann cells in PNS that forms only one intermodal flap of myelin

Microscopy:
Light: nucleus is small and round with dense clumps of heterochromatin
o May be position next to neurons (perineuronal) or in rows along bundles of nerve fibers
(interfascicular)
EM: dense clumps of chromatin seen in the nucleus; cytoplasm is electron dense due to the presence of
numerous organelles and a proteinaceous matrix between the organelles; numerous microtubules but no glial
filaments
MICROGLIA:

Basics:
Comprise 5-10% of all neuroglia
Found in both white and gray matter (particularly associated with blood vessels)

Microscopy:
Light: small cell body is elongated with a few short and irregular processes, covered with barbed-wire-like
appendages

Function:
Resting State: mostly static
Immunologically Activate: in injury or disease; undergo rapid proliferation and migration toward pathologic foci
where they transform into macrophages
o Strongly phagocytic- ingest neuronal debris that has resulted from injury or disease (cells engorged
with neuronal debris called gitter cells)
o Some of these functions shared with migrating monocytes from the blood
EPENDYMA/TANYCYTES:

Function:
Form the continuous lining of the ventricular cavities and of the central canal of the spinal cord
Produced a small amount of CSF in the ventricles

Shape/Structure:
Varies from cuboidal to columnar depending on the brain region
Apical surface (facing lumen of ventricles) has numerous microvilli and motile cilia
Membranes of adjacent cells form both gap and adhesion-type junctions (no tight junctions exist here)
o Existing Barriers:

Between blood and brain (BBB)

Between blood and CSF
o Note that there is NO barrier between CSF and brain

Choroidal Ependyma: form part of the choroid plexus and form most of the CSF in the ventricles
o Mostly cuboidal cells
o Tight junctions found at the apex of adjacent cells (CSF-blood barrier)
o Blood vessels of choroid plexus are fenestrated
o
ATPase pumps in both apical and basilar membranes of choroidal ependyma cells critical in the formation
and final composition of CSF

Tanycytes: specialized ependyma with long processes extending from the base of the cell body to blood vessels in the
adjacent neuropil or to the pial surface
o Found in small patches in circumventricular organs (ie. median eminence, area postrema, pituitary gland)
where there is no BBB
o May absorb and transport releasing hormones from CSF to circulation
SCHWANN CELL:

Myelin Producing Cells of PNS:
Maintains only one intermodal myelin segment in mature myelinated fibers
Also forms the sheath for unmyelinated axons in the PNS
o May form the sheath for as many as 20 unmyelinated axons (usually C fibers for pain and autonomic
axons)
Role in Developing PNS Axons:
o Schwann cells first align along an axon
o Elongation and spiraling of the membranes around the axon ultimately results in opposing membranes
with a distinct periodicity
DIFFERENCE BETWEEN CENTRAL AND PERIPHERAL MYELIN:

CNS: results from the compaction of the oligodendrocyte membranes

PNS: results from the compaction of the Scwann cell membranes

Similarities: in both, spaces between intermodal segments are called nodes of Ranvier (allow for saltatory impulse
conduction)

Differences:
o CNS: nodes are covered by astrocyte processes
o PNS: nodes covered by both cytoplasmic extension of the adjacent Schwann cells and by a basal lamina
outside the Schwann cell membrane

Basal lamina plays a role in PNS axon regeneration following a nerve injury
o CNS and PNS myelin have different molecular compositions and immunological properties
RELEVANCE TO HUMAN DISEASE:

Most brain tumors are of glial origin: neuronal tumors are extremely rare

Astrocytomas: astroglia-derived tumors; glioblastoma multiformis is very malignant

Ependymoma: ependyma-derived tumors; originate from the ependyma lining the ventricles, but later invade the
underlining brain parenchyma

Schwannoma: tumor of Schwann cells in the PNS
o Example: acoustic neuroma- begins in the nerve fibers of CNVIII close to the cerebellopontine angle

Oligodendrogliomas: rare

Multiple Sclerosis: oligodendrocytes are involved; autoimmune response to one of the proteins in central myelin
o More prevalent in females than males
o Rare in countries close to the equator
o Sclerotic plaques form randomly throughout the brain and brainstem, particularly in heavily myelinated
tracts of the white matter
o Treatments include anti-inflammatory drugs (ie. steroids) and interferon beta