ScussionThe results of our study demonstrate that tau may have a functional role in the expression of sexual Madecassoside site behavior in the absence of gonadal steroids and perhaps the morphological differences we noted in neurons of the MPOA. Gonadal steroids, both androgens and estrogens, have a profound impact on dendritic morphology and patterns of synaptic connectivity in the adult central nervous system (reviewed in [24]). This is evident not only in brain areas classically associated with learning and memory, but in brain areas involved in the control of sexually dimorphic behaviors [25?7]. The results of these studies lend support to the hypothesis that MSB may be regulated by gonadal steroids in adulthood by promoting synaptic remodeling. However, unlike any of these studies in which the neuronal modifications were dependent upon steroidal action, the increased number of dendritic spines evidenced in the maters in our study correlate with striking differences in behavior independent of gonadal steroids. Our characterization of the dendritic architecture between maters and non-maters in MPOA neurons are similar to results from previous studies that have investigated changes in dendritic morphology in the dorsal CA1 region of the hippocampus, albeit in response to gonadal hormones. These studies reported that hormone-induced changes in spine density reflect differences in spine number, rather than changes in dendritic length or branching [28] or axodendritic synapse density [29]. Notably, steroid replacement treatment (with either testosterone propionate or estradiol benzoate) is sufficient to restore MSB in non-maters [30]. It remains to be determined whether administration of exogenous steroids is sufficient to induce spinogenesis in nonmaters. In light of the well-characterized ability of estradiol toregulate plasticity by affecting dendritic structure, particularly spinogenesis, in the neural circuitry underlying female sexual behavior, it is likely that gonadal steroids may regulate MSB through similar mechanisms [31]. Several lines of evidence 18055761 now indicate that increased tau 223488-57-1 biological activity levels are functionally associated with steroid-independent MSB. Tau levels in the MPOA were higher in hybrid maters relative to nonmaters, confirming the results of earlier gene expression data showing elevated MAPT expression in the MPOA of maters relative to non-maters [9]. Similar to the APP overexpressing mice, facilitation of mounting or intromitting behavior in a significant proportion of the tau overexpressors persisted for two months after orchidectomy relative to littermate controls. They did not display ejaculations beginning 10 weeks after orchidectomy, whereas a high percentage of orchidectomized B6D2F1 hybrid male mice were demonstrating this behavior well beyond 10 weeks after orchidectomy in previous reports [5,7]. The relative decreased proportion of mice displaying ejaculations observed in the tau overexpressors may be caused by genetic background, as they were bred onto the C57BL/6J inbred-strain which normally does not demonstrate steroid-independent MSB. Additionally, it is likely that MSB is maintained by a combination of genes, and here we only manipulated one, MAPT. In addition to MAPT, there were three other microtubule-associated protein genes from the microarray analyses that were differentially expressed between B6D2F1 hybrid maters and non-maters. Similar to MAPT, microtubule-associated protein RP/EB family, member 3 (MAPRE3), microtubule-a.ScussionThe results of our study demonstrate that tau may have a functional role in the expression of sexual behavior in the absence of gonadal steroids and perhaps the morphological differences we noted in neurons of the MPOA. Gonadal steroids, both androgens and estrogens, have a profound impact on dendritic morphology and patterns of synaptic connectivity in the adult central nervous system (reviewed in [24]). This is evident not only in brain areas classically associated with learning and memory, but in brain areas involved in the control of sexually dimorphic behaviors [25?7]. The results of these studies lend support to the hypothesis that MSB may be regulated by gonadal steroids in adulthood by promoting synaptic remodeling. However, unlike any of these studies in which the neuronal modifications were dependent upon steroidal action, the increased number of dendritic spines evidenced in the maters in our study correlate with striking differences in behavior independent of gonadal steroids. Our characterization of the dendritic architecture between maters and non-maters in MPOA neurons are similar to results from previous studies that have investigated changes in dendritic morphology in the dorsal CA1 region of the hippocampus, albeit in response to gonadal hormones. These studies reported that hormone-induced changes in spine density reflect differences in spine number, rather than changes in dendritic length or branching [28] or axodendritic synapse density [29]. Notably, steroid replacement treatment (with either testosterone propionate or estradiol benzoate) is sufficient to restore MSB in non-maters [30]. It remains to be determined whether administration of exogenous steroids is sufficient to induce spinogenesis in nonmaters. In light of the well-characterized ability of estradiol toregulate plasticity by affecting dendritic structure, particularly spinogenesis, in the neural circuitry underlying female sexual behavior, it is likely that gonadal steroids may regulate MSB through similar mechanisms [31]. Several lines of evidence 18055761 now indicate that increased tau levels are functionally associated with steroid-independent MSB. Tau levels in the MPOA were higher in hybrid maters relative to nonmaters, confirming the results of earlier gene expression data showing elevated MAPT expression in the MPOA of maters relative to non-maters [9]. Similar to the APP overexpressing mice, facilitation of mounting or intromitting behavior in a significant proportion of the tau overexpressors persisted for two months after orchidectomy relative to littermate controls. They did not display ejaculations beginning 10 weeks after orchidectomy, whereas a high percentage of orchidectomized B6D2F1 hybrid male mice were demonstrating this behavior well beyond 10 weeks after orchidectomy in previous reports [5,7]. The relative decreased proportion of mice displaying ejaculations observed in the tau overexpressors may be caused by genetic background, as they were bred onto the C57BL/6J inbred-strain which normally does not demonstrate steroid-independent MSB. Additionally, it is likely that MSB is maintained by a combination of genes, and here we only manipulated one, MAPT. In addition to MAPT, there were three other microtubule-associated protein genes from the microarray analyses that were differentially expressed between B6D2F1 hybrid maters and non-maters. Similar to MAPT, microtubule-associated protein RP/EB family, member 3 (MAPRE3), microtubule-a.