Localization and developmental ontogeny of the pro-apoptotic Bnip3 mRNA in the postnatal rat cortex and hippocampus.

Naturally occurring cell death occurs during the first two postnatal weeks in the rat cortex and hippocampus. During this process, apoptosis is initiated by activating or altering expression of pro-apoptotic members of the Bcl-2 family. Bnip3 is a pro-apoptotic member of the Bcl-2 family that induces cell death by opening the mitochondrial permeability transition pore. To date, Bnip3 expression in the central nervous system has only been examined during hypoxia-mediated apoptosis in the adult rat brain. In this study, we investigated the localization and ontogeny of Bnip3 mRNA expression in the postnatal male and female rat brain. Bnip3 mRNA was localized by in situ hybridization in the neonatal cortex, hippocampus, habenula and thalamus. Using quantitative real-time RT-PCR, Bnip3 mRNA levels were found to be greatest at postnatal day 6.5 in the female anterior and posterior cingulate cortices and hippocampus. Bnip3 mRNA expression also increased in the male anterior cingulate cortex at postnatal day 6.5. However, a developmental change in Bnip3 levels did not occur in the male posterior cingulate cortex and hippocampus. In the anterior cingulate cortex on postnatal day 6.0 and adulthood, female rats had significantly greater levels of Bnip3 mRNA compared to that of males. Altering levels of testosterone in the neonatal rat did not alter the sex differences in Bnip3 mRNA levels. The transient increase in Bnip3 mRNA expression correlates with naturally occurring cell death in the neonatal rat cortex and hippocampus. Thus, Bnip3 may be a mediator of developmental apoptosis in the postnatal rat brain.