http://www.sciencedirect.com/science/article/pii/S0197018612001271
Abstract
Our
previous experiments suggest that treatment with Bcl-2 increases
proliferation and differentiation of neuronal progenitors induced by
ischemic injury and ameliorates neurological functional deficits after
stroke. However, in addition to its traditional anti-apoptotic effect,
little is known about the concrete molecular modulation mechanism. In
this study, Bcl-2-expressing plasmids were injected into the lateral
ventricle of rat brains immediately following a 30-min occlusion of the
middle cerebral artery to determine the role of Bcl-2 in adult
neurogenesis. Bcl-2 overexpression reduced ischemic infarct and
astrogenesis, and enhanced ischemia-induced striatal neurogenesis. We
further found that Bcl-2 increased β-catenin, a key mediator of
canonical Wnt/β-catenin signaling pathway, and reduced bone
morphogenetic proteins-4 (BMP-4) expression in the ipsilateral striatum
following ischemia. Treatment of stroke with β-catenin siRNA (i.c.v)
showed that β-catenin siRNA antagonized Bcl-2 neuroprotection against
ischemic brain injury. More interestingly, β-catenin siRNA
simultaneously abolished Bcl-2-mediated reduction of BMP-4 expression
and enhancement of neurogenesis in the ipsilateral striatum. This effect
is independent of Noggin, the known BMP antagonist. These findings
highlight a new regulatory mechanism that Bcl-2 elevates
ischemia-induced striatal neurogenesis by down-regulating expression of
BMP-4 via activation of the Wnt/β-catenin signaling pathway in adult rat
brains.
Highlights
►
Bcl-2 enhanced stroke-induced neurogenesis in adult rat brains. ► Bcl-2
increased β-catenin and reduced BMP-4 in ischemic injured brains. 3.
β-catenin siRNA abolished Bcl-2-enhanced stroke-induced neurogenesis. 4.
β-catenin siRNA antagonized Bcl-2-reduced BMP-4 function in ischemic
injured brains. ► Bcl-2 increased neurogenesis by inhibiting BMP-4 via
activation of Wnt signaling.
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