http://www.jneurosci.org/content/33/3/1241.short
Abstract
Appropriately targeted manipulation of
endogenous neural stem progenitor (NSP) cells may contribute to
therapies for trauma,
stroke, and neurodegenerative disease. A
prerequisite to such therapies is a better understanding of the
mechanisms regulating
adult NSP cells in vivo. Indirect data
suggest that endogenous ciliary neurotrophic factor (CNTF) receptor
signaling may inhibit neuronal differentiation
of NSP cells. We challenged subventricular zone
(SVZ) cells in vivo with low concentrations of CNTF to
anatomically characterize cells containing functional CNTF receptors. We
found that type
B “stem” cells are highly responsive, whereas
type C “transit-amplifying” cells and type A neuroblasts are remarkably
unresponsive,
as are GFAP+ astrocytes found outside the SVZ. CNTF was identified in a subset of type B cells that label with acute BrdU administration.
Disruption of in vivo CNTF receptor
signaling in SVZ NSP cells, with a “floxed” CNTF receptor α (CNTFRα)
mouse line and a gene construct driving
Cre recombinase (Cre) expression in NSP cells,
led to increases in SVZ-associated neuroblasts and new olfactory bulb
neurons,
as well as a neuron subtype-specific,
adult-onset increase in olfactory bulb neuron populations. Adult-onset
receptor disruption
in SVZ NSP cells with a recombinant
adeno-associated virus (AAV-Cre) also led to increased neurogenesis.
However, the maintenance
of type B cell populations was apparently
unaffected by the receptor disruption. Together, the data suggest that
endogenous
CNTF receptor signaling in type B stem cells
inhibits adult neurogenesis, and further suggest that the regulation may
occur
in a neuron subtype-specific manner.
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