Simulated weightlessness induces hippocampal insulin resistance and cognitive impairment.
Simulated weightlessness induces hippocampal insulin resistance and cognitive impairment.
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DOI：
10.2139/ssrn.4394168
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发表时间：
2023-09
期刊：
影响因子：
6.1
通讯作者：
Jiahui Li;Caiyan Xue;Hongyan Yang;Jiaxin Zhang;Guohua Li;Jijun Li;Fang Kuang;Jing Chen
中科院分区：
文献类型：
--
作者：
Jiahui Li;Caiyan Xue;Hongyan Yang;Jiaxin Zhang;Guohua Li;Jijun Li;Fang Kuang;Jing Chen
越来越多的证据强调了长期太空飞行的潜在后果，包括灰质体积减少和认知功能障碍，宇航员中有糖尿病的亚临床表现，但其潜在机制仍不清楚。在本研究中，我们发现，长期模拟失重诱导大鼠海马胰岛素抵抗，并随后神经元损伤和认知障碍。接受4周尾部悬吊的大鼠表现出外周胰岛素抵抗，表现为空腹血糖升高、葡萄糖耐量和胰岛素耐量异常，以及自发活动减少和识别记忆受损。此外，4周模拟失重诱导海马神经元凋亡和变性，如TUNEL和Fluoro-Jade B染色阳性神经元增加所证明的。机械地，胰岛素刺激的海马Akt磷酸化减少，而胰岛素信号的负调节因子PTEN在尾悬吊大鼠海马中增加。有趣的是，小檗碱，一种胰岛素增敏剂，治疗，部分逆转上述模拟失重引起的影响。这些数据表明，长期模拟失重诱导认知障碍以及神经元凋亡和神经变性，部分通过海马胰岛素抵抗通过PTEN上调。黄连素治疗减轻海马胰岛素抵抗和改善认知功能。
Growing evidence highlights the potential consequences of long-term spaceflight, including gray matter volume reduction and cognitive dysfunction with subclinical manifestations of diabetes mellitus among astronauts, but the underlying mechanisms remain unknown. In this study, we found that long-term simulated weightlessness induced hippocampal insulin resistance and subsequent neuronal damage and cognitive impairment in rats. Rats subjected to 4-week tail suspension exhibited peripheral insulin resistance, evidenced by increased fasting blood glucose and abnormal glucose tolerance and insulin tolerance, alongside reduced spontaneous activity and impaired recognition memory. In addition, 4 weeks of simulated weightlessness induced neuronal apoptosis and degeneration in the hippocampus, as evidenced by increased TUNEL and Fluoro-Jade B staining-positive neurons. Mechanistically, insulin-stimulated hippocampal Akt phosphorylation was decreased, while PTEN, the negative regulator of insulin signaling, was increased in the hippocampus in tail-suspended rats. Interestingly, treatment with berberine, an insulin sensitizer, partly reversed the above-mentioned effects induced by simulated weightlessness. These data suggest that long-term simulated weightlessness induces cognitive impairment as well as neuronal apoptosis and neural degeneration, partially through hippocampal insulin resistance via PTEN up-regulation. Berberine treatment attenuates hippocampal insulin resistance and improves cognitive function.