Page 124 - Read Online

in several neurodegenerative diseases including
Alzheimer’s disease (AD). In later alterations of AD,
senile plaques trigger glial reactivity that, in turn,
advances neuronal death and cognitive deficit. Recently,
it has been demonstrated that reactive astrocytes
produce the inhibitory gliotransmitter GABA, which
in consequence reduces the synaptic plasticity and
the performance of learning and memory in a mouse
Figure 1: Immunofluorescence images of parenchymal astrocytes. Astrocytic model of AD. [17] Nevertheless, the role of astrocytes in
processes in the adult human brain are more profuse and thinner than in the the pathogenesis or progression of neurodegenerative
rodent or fetal brain, glial fibrillary acidic protein
diseases is not completely understood.
in a number of neuronal and glial functions. Up- or
down-regulation of different phosphoinositide-specific A subpopulation of astrocytes can also function as
PLC isoforms (PI) can drive astrocyte reactivity associated neural stem cells in the adult’s brain. Neural stem
with brain inflammation and tumor progression. [13] cells reside in the ventricular-SVZ (V-SVZ), a cell
PI-PLC β1, PI-PLC β4 and PI-PLC 1 have been found in niche lining the lateral wall of the lateral ventricles. [18]
reactive astrocytes, whereas PI-PLC β3, PI-PLC 2, PI-PLC Therein a subpopulation of astrocytes functions as
2, PI-PLC PI-PLC have been identified in brain tumor bona fide neural stem cells that generate a number
cells (astrocytoma). However, the clinical significance of of neuroblasts that rostrally migrate and differentiate
these findings remains to be clarified. [14] In this regard, into interneurons at the olfactory bulb. [18] V-SVZ
the expression of nicotinamide adenine dinucleotide astrocyte progenitors can also promote the genesis
+
phosphate -dependent isocitrate dehydrogenase-1 of oligodendrocytes that populate white matter tracts
gene and epidermal growth factor (EGF) appear to of corpus callosum and striatum. [19] Interestingly,
distinguish reactive astrocytes from glioma, but further the intraventricular administration of EGF increases
validation is required to confirm these findings. [15] dramatically the production of V-SVZ oligodendrocytes
and NG2-platelet-derived growth factor receptor-α
Neurotropic viruses are infectious particles that can expressing cells, which temporarily disrupt the
preferentially infect neural cells by evading the brain neighboring white matter. [19] Oligodendrocyte
immune response and infecting astroglia. Such viral dysfunction has been found across most psychiatric
infection in astrocytes alters their functions and lead conditions, including mood disorders. [20] However, the
to serious neural damages with severe neurological role of V-SVZ oligodendrogenesis in the pathophysiology
complications. In response to the viral infection, current of neuropsychiatric disorders remains to be elucidated.
evidence indicates that activated astrocytes promote
innate immune response through the expression of In the adult hippocampus, another subpopulation of
toll-like receptors and secretion of cytokines, that astrocytes gives rise to new neurons that populate the
[21]
is, astrocytes appear to direct immune response and granular layer of the dentate gyrus. These multipotent
neuroinflammation. [13] astrocytes help control several behavioral tasks, such as
episodic-like and spatial memory, object recognition tasks
[22]
+
Astrocytes contain inward-rectifier K (Kir) channels and cognitive performance. Interestingly, morphological
+
that efficiently maintain potassium (K ) homeostasis changes and local distribution of astrocytes are dependent
[16]
during neuronal activities. Changes in the expression on aging and enriched environments. Therefore, astrocytic
and functioning of astrocytic Kir channels modify neural stem cells in the V-SVZ and dentate gyrus help
K spatial buffering. The reduced Kir4.1 channel preserve cellular homeostasis and exert modulatory roles
+
expression or Kir4.1 channel misallocations promote on neural circuitry in the adult’s brain.
astrocyte depolarization, which decreases their ability
to clear extracellular glutamate. This mechanism is Astrocytes not only preserve the oligodendrocyte
responsible for the neural damage in epilepsy and population, [23] but also modulate the myelination
ischemia. Hence, novel therapeutic approaches have process of oligodendrocytes. [24] Some mutations in
+
been suggested to involve the regulation of K spatial astrocytes are associated with leukodystrophies, a
buffering by astrocytes. group of neurological disorders characterized by
imperfect myelin ensheathing. Therefore, although the
Since astrocytes are responsible for the optimal ionic origin of megalencephalic leukoencephalopathy was
homeostasis and neurotransmission balance, astrocytic initially related to the malfunction of oligodendrocyte,
atrophy has been associated with early alterations of the emerging evidence indicates that the pathophysiology
neuronal transmission and synaptic networks observed is associated with astrocytic dysfunction.

116 Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015