Off-campus UMass Amherst users: To download dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users, please click the view more button below to purchase a copy of this dissertation from Proquest.
(Some titles may also be available free of charge in our Open Access Dissertation Collection, so please check there first.)
The role of Bcl-2 family members in sexual differentiation and adult neural plasticity
Hormonal control of developmental cell death is the best-established mechanism of neural sexual differentiation. For example, the spinal nucleus of the bulbocavemosus (SNB) is a sexually-dimorphic cluster of motoneurons in the lumbar spinal cord that innervates perineal muscles. Testosterone acts during a perinatal critical period to reduce cell death, and as a result, male rodents have more and larger SNB motoneurons than do females. Conversely, testosterone increases cell death in the anteroventral penventricular nucleus (AVPV), making it larger in females than in males. The Bcl-2 family of proteins has been implicated in mediating developmentally-regulated cell death. The ratio of pro-life (e.g., Bcl-2) to pro-death (e.g., Bax) family members apparently determines a cell's fate. We found that Bcl-2 overexpression increased neuron number in the SNB of females and in the AVPV of males. By contrast, Bcl-2 overexpression increased cell number equally in both sexes in the retrodorsolateral nucleus (RDLN), a spinal nucleus in which cell number is neither sexually dimorphic nor affected by perinatal hormone treatments. An immunocytochemical analysis indicated that Bcl-2, Bcl-xL and Bax are normally present in SNB motoneurons during the perinatal critical period, although their role in mediating SNB apoptosis is unclear. In adulthood, testosterone no longer determines SNB motoneuron survival, but does regulate soma size and dendritic extent. The continued expression of Bcl-2 family members in some neurons after the cell death period suggests additional roles beyond the regulation of cell death. I found that castration of adult male rats reduced Bcl-2 immunoreactivity in SNB motoneurons, and this reduction could be prevented by testosterone; Bax expression was not affected. Although the adult plasticity of SNB motoneurons is well characterized in rats, it has not been elucidated in mice. Four weeks following castration, soma size and dendritic extent shrink in rat SNB motoneurons. However, we showed that in the B6D2F1 strain of mouse, soma size decreased 6 and 12 weeks following castration, but dendritic extent remained unchanged. In addition, although Bcl-2 appears to be regulated by testosterone in the SNB motoneurons of adult rats, overexpression of Bcl-2 could not compensate for castration-induced soma size changes in the mouse SNB.
Zup, Susan L, "The role of Bcl-2 family members in sexual differentiation and adult neural plasticity" (2002). Doctoral Dissertations Available from Proquest. AAI3056297.