Although hippocampus-derived androgens play an important role in hippocampal synaptic plasticity, studies at the cellular level have received relatively less attention. Furthermore, the underlying signalling pathways associated with synaptic plasticity remain unclear. Results of the present study demonstrated that testosterone treatment of primary cultured rat hippocampal neurons resulted in a rapid increase in spine density, accompanied by the elevation of protein and messenger RNA levels of synaptophysin, developmentally regulated brain protein (Drebrin), and the N-methyl-D-aspartate receptor NR1 subunit. Testosterone treatment also increased the phosphorylation levels of extracellular-regulated protein kinase (ERK)1/2 and cAMP-responsive element binding protein (CREB), rather than p38 and Jun N-terminal kinase (JNK). U0126 significantly reversed the testosterone-mediated phosphorylation of CREB. Importantly, the increase in spine density was not induced by testosterone under U0126 treatment. These findings suggest that the ERK1/2-CREB signalling pathway plays an important role in testosterone-mediated rapid spinogenesis of cultured rat hippocampal neurons. Results of this study will be helpful in further clarifying the physiological function of testosterone and related signalling pathways in vitro.

中文翻译：

---

睾丸激素通过ERK-CREB信号通路调节原代培养海马神经元的结构突触可塑性。

尽管海马来源的雄激素在海马突触可塑性中起着重要作用，但在细胞水平的研究却相对较少受到关注。此外，与突触可塑性相关的潜在信号传导途径仍不清楚。本研究结果表明，睾丸激素治疗原代培养的大鼠海马神经元可导致脊柱密度快速增加，伴有突触素的蛋白质和信使RNA水平升高，发育调节的脑蛋白（Drebrin）和N-甲基-D-天冬氨酸受体NR1亚基。睾丸激素治疗还增加了细胞外调节蛋白激酶（ERK）1/2和cAMP反应元件结合蛋白（CREB）的磷酸化水平，而不是p38和Jun N端激酶（JNK）的磷酸化水平。U0126显着逆转了睾丸激素介导的CREB磷酸化。重要的是，在U0126处理下，睾丸激素不会引起脊柱密度的增加。这些发现表明，ERK1 / 2-CREB信号通路在睾丸激素介导的大鼠海马神经元快速自旋发生中起重要作用。这项研究的结果将有助于进一步阐明睾丸激素的生理功能和相关的体外信号通路。