BRAIN TISSUE TRANSPLANTS AND REPRODUCTIVE PROCESSES

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Although brain tissue transplantation in rats has recently been used to investigate the development and potential for functional integration of transplanted brain regions, exploring reproductively-important brain processes with this new research tool has not yet been cohesively addressed. In this regard, little is known about the exact mechanism(s) by which gonadal hormones (such as testosterone) organize or alter the development of the mammalian brain to bring about its sexual and neuroanatomical differentiation. Therefore, the studies of this proposal's first section will attempt to elucidate the mechanism(s) of steroid action on the brain by investigating the effects of testosterone on the development of immature, male brain tissue after its transplantation into the brain of recipient female neonates. Particular emphasis will be given to possible gonadal steroid effects on the survival of transplanted neurons, their neuroanatomical structure, and their potential for migration. As a challenge for brain tissue transplants to alter the neural functions of recipient animals, the studies of this proposal's second section will test the ability of transplanted male brain tissue to establish functional connectivity with the host female brains, as evidenced by transplant-induced alterations in the recipient animals' sexual behavior and Luteinizing Hormone secretory patterns. If such modifications in brain functions are observed, strong evidence will have been provided not only for the functional integration of transplanted tissue, but for the feasibility of using brain tissue transplants clinically to restore normal function to damaged or diseased brain areas. The studies of this proposal involve a new intraparenchymal transplantation technique designed to discretely place transplanted brain tissue intothe most natural environment for its normal development and establishment of functional connectivity. As such, this proposal represents the first full-scale attempt to investigate the development and function of brain reproductive mechanisms through the use of brain tissue transplantation.