Faculty of Medicine, Department of Physiology, Erciyes University, Kayseri, Turkey.
Physiol Behav. 2022 Oct 15;255:113939. doi: 10.1016/j.physbeh.2022.113939. Epub 2022 Aug 9.
The present study investigates sex differences in hippocampal functions in the context of synaptic plasticity, which is the cellular basis of learning and memory, and differences in the mitogen-activated protein kinase (MAPK) pathway that accompanies plasticity in young-adult rats. The long-term potentiation (LTP) and long-term depression (LTD) were induced by stimulating the perforant pathway (PP) and field potentials composed of the field excitatory post-synaptic potential (fEPSP) and population spike (PS) were recorded from the dentate gyrus (DG). Following the completion of the electrophysiological recordings, the hippocampi were removed bilaterally, and the protein and gene expression levels of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and P38-MAPK were determined by Western blot analysis and real-time PCR, respectively. No significant difference was found in synaptic and neuronal function before (basal) and after high-frequency stimulation between male and female rats. Nevertheless, female, but not male, rats were able to express long term depression at the PP - DG synapses, suggesting that sex differences in plasticity are stimulation paradigm specific. MAPK1 expression was higher in males and MAPK3 expression was higher in females, but these differences disappeared after induction of plasticity in both sexes. While the expression of MAPK8 is influenced by sex, independent of the induction of plasticity, MAPK14 expression was down regulated by plasticity induction in females, but not males. No effect of sex, HFS and LFS on total and phosphorylated levels of MAPKs was found except phosphorylated ERK1/2. Phosphorylation of ERK1/2 was up regulated after LFS in male rats but did not change in female rats. These findings indicate that LFS-induced plasticity is differentially modulated between sexes, probably as a result of increased activation of ERK1/2 in male rats.
本研究在突触可塑性的背景下研究了海马功能的性别差异，突触可塑性是学习和记忆的细胞基础，以及伴随年轻成年大鼠可塑性的丝裂原活化蛋白激酶 (MAPK) 途径的差异。通过刺激穿通途径 (PP) 诱导长时程增强 (LTP) 和长时程抑制 (LTD)，并从齿状回 (DG) 记录由场兴奋性突触后电位 (fEPSP) 和群体锋电位 (PS) 组成的场电位。在完成电生理记录后，双侧取出海马体，并通过 Western blot 分析和实时 PCR 分别确定细胞外信号调节激酶 1/2 (ERK1/2)、c-Jun N-末端激酶 (JNK) 和 P38-MAPK 的蛋白和基因表达水平。在高频刺激前后，雄性和雌性大鼠的突触和神经元功能在基础水平上没有差异。然而，只有雌性大鼠而不是雄性大鼠能够在 PP-DG 突触处表达长时程抑制，这表明可塑性的性别差异是刺激范式特异性的。MAPK1 的表达在雄性中较高，MAPK3 的表达在雌性中较高，但这些差异在两性诱导可塑性后消失。虽然 MAPK8 的表达受性别影响，但与诱导可塑性无关，MAPK14 的表达在诱导可塑性后在雌性中下调，但在雄性中没有下调。除磷酸化 ERK1/2 外，性别、HFS 和 LFS 对 MAPKs 的总水平和磷酸化水平均无影响。磷酸化 ERK1/2 在雄性大鼠 LFS 后上调，但在雌性大鼠中没有变化。这些发现表明，LFS 诱导的可塑性在性别之间存在差异调节，可能是由于雄性大鼠 ERK1/2 的激活增加所致。
