Sex and Age Differences in Apoptosis in the Developing Mouse Hippocampus and Cerebral Cortex

Export Programmed cell death, or apoptosis, is a critical mechanism contributing to the development of sex differences in cell number within specific regions of the vertebrate brain. While apoptosis has been previously documented in the developing mouse hippocampus and cerebral cortex, detailed analyses comparing both sexes have been limited. In this study, we performed immunohistochemistry for activated caspase-3, a marker of apoptosis, to quantify the distribution of apoptotic cells across subregions of the mouse hippocampus and surrounding cortex at postnatal (PN) days 0 and 7. In addition, we assessed the expression of preselected apoptosis-related genes in the developing hippocampus and cortex using Qiagen’s polymerase chain reaction (PCR) arrays and reverse transcription quantitative PCR. Our findings revealed that, during early development, male mice exhibited a higher number and/or density of activated caspase-3 cells in the stratum pyramidale of the cornu ammonis (CA) 1, the stratum oriens of the CA3, and the polymorphic layer of the dentate gyrus. We also observed widespread, age-dependent changes in apoptosis across various hippocampal and cortical subregions. Furthermore, while no sex differences were detected in gene expression, we observed an age-dependent decrease in the expression of Akt1 and Bok mRNA in the developing hippocampus and cortex. Together, our findings reveal region-specific patterns of apoptosis in the developing mouse hippocampus and cortex, influenced by age and sex, and identify apoptotic genes that may play a critical role in the neural development of these brain regions through transcriptional regulation.