Neurogenesis diminishes with aging and ischemia-induced neurogenesis also
occurs, but reduced in aged brain. Currently, the cellular and molecular
pathways mediating these effects remain largely unknown. Our previous study has
shown that Notch1 signaling regulates neurogenesis in subventricular zone (SVZ)
of young-adult brain after focal ischemia, but whether a similar effect occurs
in aged normal and ischemic animals is unknown. Here, we used normal and
ischemic aged rat brains to investigate whether Notch1 signaling was involved
in the reduction of neurogenesis in response to aging and modulates neurogenesis
in aged brains after focal ischemia. By Western blot, we found that Notch1 and
Jagged1 expression in the SVZ of aged brain was significantly reduced compared
with young-adult brain. Consistently, the activated form of Notch1(Notch
intracellular domain;NICD) expression was also declined. Immunohistochemistry
confirmed that expression and activation of Notch1 signaling in the SVZ of aged
brain were reduced. Double or triple immunostaining showed that that Notch1 was
mainly expressed in DCX-positive cells, whereas Jagged1 was predominantly
expressed in astroglial cells in the SVZ of normal aged rat brain. In addition,
disruption or activation of Notch1 signaling altered the number of proliferating
cells labeled by bromodeoxyuridine (BrdU) and doublecortin (DCX) in the SVZ of
aged brain. Moreover, ischemia-induced cell proliferation in the SVZ of aged
brain was enhanced by activating the Notch1 pathway, and was suppressed by
inhibiting the Notch1 signaling. Reduced infarct volume and improved motor
deficits were also observed in Notch1 activator-treated aged ischemic rats. Our
data suggest that Notch1 signaling modulates the SVZ neurogenesis in aged brain
in normal and ischemic conditions.