Sexual differentiation is a critical developmental process that results in differences in brain structure and function between the sexes. In mice, two surges of testosterone are secreted by the developing testes during late embryonic stage and on the day of birth which masculinize brain structure and function via direct activation of androgen receptors (AR) and/or indirect activation of estrogen receptors (ERs), ERα and ERβ, after testosterone is converted to estradiol locally by aromatase. However, the downstream effector of AR and ERs remains unknown.
SFSWAP is a splicing protein that regulates the splicing of microtubule-associated protein tau, and accumulation of tau in neurofibrillary tangles is found in Alzheimer's disease brain. Alzheimer's disease is a neurodegenerative disorder that affects the function of the hippocampus, and women are more likely to develop this disease than men. Since sex steroid-mediated brain sexual differentiation may confer the sex difference in risk or resilience to Alzheimer's diseases, I hypothesized that during early development, SFSWAP expression in the mouse hippocampus was sexually dimorphic, and was regulated by the perinatal rises in circulating testosterone via the activation of AR and/or ERs. To test this, I utilized immunohistochemistry to detect and measure SFSWAP-immunoreactive (ir) cells in the hippocampus of three mouse models at 21 days of age: untreated male and female C57BL/6J mice, testicular feminized mice with mutated AR and their wild-type littermates, and male and female mice neonatally treated with vehicle or estradiol benzoate (EB). My results demonstrated that (1) female mice showed a higher SFSWAP cell density in the CA1 and CA3, not dentate gyrus (DG), of the hippocampus than males, (2) AR mutation increased SFSWAP-ir cells in the CA1, not the CA3 nor the DG, and (3) neonatal treatment of EB increased SFSWAP cell number in the CA3, not CA1 or DG, of male and female mice. My study suggests that activation of AR by perinatal testosterone may reduce the SFSWAP cell number in the CA1, which might contribute to sex differences in the hippocampal structure and function.
|Commitee:||Sinchak, Kevin, Zavala, Arturo|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 58/05M(E), Masters Abstracts International|
|Subjects:||Neurosciences, Endocrinology, Physiology, Developmental biology|
|Keywords:||Hippocampus, Hormones, Immunohistochemistry, Mouse, Sex, Sfswap|
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