RESUMO
The magnocellular medial preoptic nucleus (MPN mag), a subdivision of the medial preoptic area (MPOA), plays a critical role in the regulation of copulation in the male Syrian hamster; in part by mediating the effects of gonadal steroids. For example, ablation of the MPN mag eliminates mating and testosterone placed in the MPN mag restores mating in castrated males. Furthermore, testosterone treatment enhances synaptic density and dendritic spines in the MPN mag. Thus, copulatory behaviors are correlated with increases in synaptic morphology in the MPN mag. As brain derived neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase-B (TrkB), effect neuronal growth and synaptic plasticity, this study explored the role of TrkB and BDNF in mediating testosterone's effects on the MPN mag and behavior. Testosterone treatment increased BDNF expression and conversely lowered TrkB expression in the MPOA. siRNA-mediated TrkB knockdown in the MPN mag eliminated copulation two-days post injection and the behavior was restored one week later. These data indicate that testosterone influences the expression of BDNF and TrkB in the MPOA and that expression of copulation is dependent on the presence of TrkB. Taken together our findings support a role for TrkB and BDNF in mediating the effects of testosterone on copulatory behavior in the Syrian hamster.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Copulação/fisiologia , Área Pré-Óptica/metabolismo , Receptor trkB/metabolismo , Reprodução/fisiologia , Testosterona/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Copulação/efeitos dos fármacos , Cricetinae , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Masculino , Mesocricetus , Área Pré-Óptica/efeitos dos fármacos , RNA Interferente Pequeno , Receptor trkB/genética , Reprodução/efeitos dos fármacosRESUMO
Testosterone plays a key role in the expression of male sex behavior by influencing cellular activity and synapses within the magnocellular medial preoptic nucleus (MPN mag), a sub-nucleus of the medial preoptic area (MPOA) in the Syrian hamster. Although the mechanisms underlying hormonally-induced synaptic plasticity in this region remain elusive, the data suggests that an increase in synaptic density may mediate testosterone's effects on copulation. As brain derived neurotrophic factor (BDNF) plays an integral role in regulating synaptic plasticity and gonadal steroids regulate the levels of BDNF, we hypothesize that BDNF may mediate the effects of gonadal hormones on copulatory behavior. To test this hypothesis, we infused BDNF or controls into the MPN mag of long-term castrates. Our results indicate that BDNF, but not the controls, restored copulatory behavior in castrated male Syrian hamsters. Furthermore, the rise of BDNF expression in the MPOA preceded the rise of synaptophysin following testosterone replacement in castrated males. These data are consistent with our hypothesis, implicating a role for BDNF in mediating testosterone's action on copulation and suggest that the delay in testosterone's restoration of copulation is, in part, due to the delay in the increase of BDNF and synaptophysin.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Copulação/efeitos dos fármacos , Orquiectomia , Área Pré-Óptica/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Cricetinae , Hormônios Esteroides Gonadais/metabolismo , Infusões Intraventriculares , Masculino , Mesocricetus , Orquiectomia/veterinária , Testosterona/metabolismoRESUMO
The cardinal symptoms of Parkinson's disease (PD) such as bradykinesia and akinesia are debilitating, and treatment options remain inadequate. The loss of nigrostriatal dopamine neurons in PD produces motor symptoms by shifting the balance of striatal output from the direct (go) to indirect (no-go) pathway in large part through changes in the excitatory connections and intrinsic excitabilities of the striatal projection neurons (SPNs). Here, we report using two different experimental models that a transient increase in striatal dopamine and enhanced D1 receptor activation, during 6-OHDA dopamine depletion, prevent the loss of mature spines and dendritic arbors on direct pathway projection neurons (dSPNs) and normal motor behavior for up to 5 months. The primary motor cortex and midline thalamic nuclei provide the major excitatory connections to SPNs. Using ChR2-assisted circuit mapping to measure inputs from motor cortex M1 to dorsolateral dSPNs, we observed a dramatic reduction in both experimental model mice and controls following dopamine depletion. Changes in the intrinsic excitabilities of SPNs were also similar to controls following dopamine depletion. Future work will examine thalamic connections to dSPNs. The findings reported here reveal previously unappreciated plasticity mechanisms within the basal ganglia that can be leveraged to treat the motor symptoms of PD.
RESUMO
Neurotrophins regulate many aspects of neuronal function and activity. Specifically, the binding of Brain-derived neurotrophic factor (BDNF) to Tyrosine receptor kinase-B (TrkB) or its truncated version, TrkB-T1, can cause growth and differentiation or dominant inhibition of receptor signaling, respectively. There is evidence that these neurotropic effects on nervous tissue, in both the central and peripheral nervous system, behave differently between the sexes. This study used western blots to examine the expression of these neurotrophins in the medial preoptic area (MPOA), a sexually dimorphic region of the hamster brain that controls male sex behavior. We report that TrkB-FL and BDNF show greater expression in male MPOA tissue, when compared to female. On the contrary, TrkB-T1 is expressed in greater abundance in the female MPOA. Our results indicate a clear sexual dimorphism of neurotrophins in the MPOA of the Syrian hamster. Furthermore, the greater expression of TrkB-FL and BDNF in the male MPOA suggests that these neurotrophins could be promoting synaptic growth to facilitate male-typical copulation. In contrast, the greater TrkB-T1 expression in the female MPOA suggests a possible inhibition of synaptic growth, and may contribute to the lack of male-typical copulation. Altogether, our data suggests that neurotrophins may play a larger role sexual differentiation than previously thought.