Molecular basis of neuronal plasticity

雄性大鼠球海绵体脊髓核的运动神经元支配着与阴茎相连的会阴横纹肌球海绵体和肛门肌。它们在交配行为中起着重要作用，这对循环中雄激素水平的变化很敏感。雄激素在雄激素敏感的SNB运动神经元的神经元元件和突触连接的重组中也起着至关重要的作用。为了阐明雄激素对神经元可塑性的分子机制，我们研究了雄性激素对成年雄性大鼠SNB运动神经元中细胞骨架蛋白（如β -肌动蛋白和β -微管蛋白）mRNA表达的调节。成年雄性大鼠被阉割，并植入含有睾酮或不含睾酮的硅胶管。4周后处死动物。鸡β -肌动蛋白和小鼠β -微管蛋白互补CNAs分别用于检测SNB运动神经元β -肌动蛋白和β -微管蛋白编码的mrna。放射性标记DNA探针应用于原位杂交组织化学。此外，还检测了支配后肢肌肉组织的背外侧后核（RDLN）中的运动神经元。β -肌动蛋白和β -微管蛋白mrna的放射自显像信号被发现定位于SNB和RDLN运动神经元的体细胞和近端树突上。通过去势去除雄激素可显著降低这些mrna在SNB运动神经元中的表达水平，而睾酮治疗可阻止这种变化。相反，阉割或睾酮治疗并没有引起雄激素不敏感的RDLN运动神经元中这些mrna表达水平的任何变化。这些结果提示雄激素调控SNB运动神经元中细胞骨架蛋白基因的表达，并可能为激素诱导SNB运动神经元神经元可塑性的分子机制提供证据。

Motoneurons of the spinal nucleus of the bulbocavornosus (SNB) of male rats innervate the perineal striated muscles bulbocavernosus and lavator ani that attach to the penis. They have an important role in copulatory behavior, which is sensitive to alterations in circulating levels of androgen. Androgen is also known to play a crucial role in reorganizing the neuronal elements and synaptic connections in androgen-sensitive SNB motoneurons. To clarify molecular mechanisms of androgen for neuronal plasticity, we examined androgenic regulation of the mRNA expression of cytoskeletal proteins such as beta-actin and beta-tubulin in the SNB motoneurons of adult male rats. Adult male rats were castrated and implanted with silastic tubes containing testosterone or nothing. Animals were sacrificed 4 weeks later. Chick beta-actine and mouse beta-tubulin complementary CNAs were used to detect mRNAs encoding beta-actin and beta-tubulin of the SNB motoneurons, respectively. The radiolabeled DNA probes were applied o in situ hybridization histochemistry. Motoneurons in the retrodorsolateral nucleus (RDLN), which innervate hindlimb musculature, were also examined. Autoradiographic signals for beta-actin and beta-tubulin mRNAs were found to be localized on the somata and proximal dendrites of SNB and RDLN motoneurons. Removal of androgen by castration significantly reduced the expression level of these mRNAs in the SNB motoneurons, whereas the change was prevented by testosterone treatment. ON the contrary, castration or testosterone treatment did not induce any changes in the expression level of these mRNAS in androgen-insensitive RDLN motoneurons. These results suggest that androgen regulates the expression of cytoskeletal protein genes in the SNB motoneurons and may provide evidence for the molecular mechanisms of hormonally-induced neuronal plasticity in the SNB motoneuron.