title: Sex-related differences in neuronal cell survival and signaling in rats.
abstract: While substantial and compelling evidence exists for sex-related differences in gross and microscopic brain structure, our understanding of the cellular mechanisms that give rise to these sexual dimorphisms is in its infancy. To investigate possible underlying mechanisms for sex-related differences in neuronal development, we examined neuronal survival and transductional signaling in male and female rat primary cortical neuronal cultures. We found that following 14 days in culture, the total number of surviving neurons was significantly higher in female cultures derived from either cortical plate (cp) or ventricular zone (vz), the regions where differentiating (cp) and proliferating (vz) cells are located. In addition, sex-related differences in the levels of phospho-ERK1 and Akt were also observed. Female cortical cultures had significantly higher levels of ERK1 in both cp and vz and higher levels of Akt in cp. No sex-related differences in Bcl-2 were observed. These data suggest that dimorphisms in cell survival may underlie enhanced neuronal survival (or decreased apoptosis) in female brain. Further, the appearance of sex-related differences at cellular and signaling levels in cortical neuronal cultures demonstrates that the effects of gender are not limited to parts of the brain mediating reproduction.
authors.affiliation: Behavioral Endocrinology Branch, National Institute of Mental Health, NIH, Building 10, Room 3N238, 10 Center Dr MSC 1276, Bethesda, MD 20892-1276, USA. zhangl@codon.nih.gov
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Pi-Peng
authors.initials: PP
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Barker
authors.forename: Susan V
authors.initials: SV
authors.lastname: Smith
authors.forename: David R
authors.initials: DR
authors.lastname: Rubinow
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D007700:Kinetics; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases