Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
Neurosci Lett. 2020 Aug 10;733:135082. doi: 10.1016/j.neulet.2020.135082. Epub 2020 May 24.
The ability to adapt to stress is an essential defensive function of a living body, and disturbance of this ability in the brain may contribute to the development of affective illness including major depression and anxiety disorders. A growing body of evidence suggests that brain serotonin (5-HT) receptors may be involved, at least in part, in the development of adaptation to stress. 5-HT receptor was reported to be transported by KIF13A, a motor protein and a member of the kinesin superfamily, from the golgi apparatus to the plasma membrane. The aim of the present study was to characterize the expression pattern of 5-HT receptor and KIF13A in the hippocampus of stress-adaptive and -maladaptive mice. Mice were either exposed to repeated adaptable (1 h/day) or unadaptable (4 h/day) restraint stress, or left in their home cage for 14 days. The levels of 5-HT receptor and KIF13A expression were assessed by western blot analysis. To confirm the formation of a 5-HT receptor and KIF13A complex, we performed blue native-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (BN-SDS-PAGE). Western blotting showed that neither 5-HT receptor nor KIF13A expression changed significantly in the hippocampal total extract of stress-adaptive and -maladaptive mice. In contrast, expression of 5 H T receptor and KIF13A in the hippocampal membrane fraction was increased in stress-adaptive mice, but not in stress-maladaptive mice. BN-SDS-PAGE analysis revealed that the bands of 5-HT receptor and KIF13A were both observed at a molecular weight of approximately 70 kDa, which indicated that 5-HT receptor and KIF13A form a complex. The present findings suggest that translocation of 5-HT receptor in complex with KIF13A to the plasma membrane of the hippocampus may play an important role in the formation of stress adaptation.
适应压力的能力是生物体的一项重要防御功能,而大脑中这种能力的紊乱可能导致包括重度抑郁症和焦虑症在内的情感疾病的发展。越来越多的证据表明,脑内 5-羟色胺(5-HT)受体可能至少部分参与了适应压力的发展。有报道称,5-HT 受体由驱动蛋白 13A(KIF13A)转运,KIF13A 是一种动力蛋白,也是驱动蛋白超家族的成员,可将 5-HT 受体从高尔基体转运到质膜。本研究旨在描述 5-HT 受体和 KIF13A 在适应和不适应压力的小鼠海马中的表达模式。将小鼠分别暴露于重复的适应性(1 小时/天)或不适应性(4 小时/天)束缚应激中,或让其在其笼中生活 14 天。通过 Western blot 分析评估 5-HT 受体和 KIF13A 的表达水平。为了确认 5-HT 受体和 KIF13A 复合物的形成,我们进行了蓝色非变性-十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(BN-SDS-PAGE)。Western blot 分析显示,适应和不适应压力的小鼠海马总提取物中 5-HT 受体和 KIF13A 的表达均无明显变化。相比之下,适应压力的小鼠海马质膜部分中 5-HT 受体和 KIF13A 的表达增加,而不适应压力的小鼠则没有。BN-SDS-PAGE 分析显示,5-HT 受体和 KIF13A 的条带均在约 70kDa 的分子量处观察到,这表明 5-HT 受体和 KIF13A 形成复合物。本研究结果表明,与 KIF13A 形成复合物的 5-HT 受体向海马质膜的易位可能在压力适应的形成中发挥重要作用。