Evidence for the spontaneous production but massive programmed cell death of new neurons in the subcallosal zone of the postnatal mouse brain

Abstract

In the last 10 years, many studies have reported that neural stem/progenitor cells spontaneously produce new neurons in a subset of adult brain regions, including the hippocampus, olfactory bulb (OB), cerebral cortex, substantia nigra, hypothalamus, white matter and amygdala in several mammalian species. Although adult neurogenesis in the hippocampus and OB has been clearly documented, its occurrence in other brain regions is controversial. In the present study, we identified a marked accumulation of new neurons in the subcallosal zone (SCZ) of Bax-knockout mice in which programmed cell death (PCD) of adult-generated hippocampal and OB neurons has been shown to be completely prevented. By contrast, in the SCZ of wild-type (WT) mice, only a few immature (but no mature) newly generated neurons were observed, suggesting that virtually all postnatally generated immature neurons in the SCZ were eliminated by Bax-dependent PCD. Treatment of 2-month-old WT mice with a caspase inhibitor, or with the neurotrophic factor brain-derived neurotrophic factor, promoted the survival of adult-generated neurons, suggesting that it is the absence of sufficient neurotrophic signaling in WT SCZ that triggers the Bax-dependent, apoptotic PCD of newly generated SCZ neurons. Furthermore, following focal traumatic brain injury to the posterior brain, SCZ neurogenesis in WT mice was increased, and a subset of these newly generated neurons migrated toward the injury site. These data indicate that the adult SCZ maintains a neurogenic potential that could contribute to recovery in the brain in response to the injury-induced upregulation of neurotrophic signaling.