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Kalirin-7 表达减少导致慢性低压缺氧暴露期间工作记忆缺陷。

Reduced expression of Kalirin-7 contributes to working memory deficit during chronic hypobaric hypoxia exposure.

机构信息

Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Luckhnow Road, Timarpur, Delhi, 110054, India.

National Institute of Pharmaceutical Education and Research (NIPER), Balanager, Hyderabad, 500037, Telangana, India.

出版信息

Behav Brain Res. 2019 Jul 2;366:135-141. doi: 10.1016/j.bbr.2019.03.016. Epub 2019 Mar 6.

DOI:10.1016/j.bbr.2019.03.016
PMID:30851319
Abstract

Hypobaric hypoxia (HH) is an environmental stress encountered at high altitude. It has been shown that HH resulted in spine atrophy and working memory deficits. Kalirin-7, a postsynaptic density protein, plays an important and key role in regulating spine dynamics and its plasticity. Spine atrophy is implicated in HH induced memory deficits but role of Kalirin-7 in this phenomenon is not studied. Present study is therefore designed to investigate the effect of chronic HH exposure on Kalirin-7 expression in hippocampus and its role in spatial working memory deficits. Adult rats (n = 12, 3 months old) were exposed to a simulated altitude of 25,000 feet for 7 days. Following HH exposure, spatial working memory was assessed with Radial arm maze and T maze. Hippocampal expression of Kalrin-7 was estimated at mRNA and protein levels. Results of behavioural experiments showed that HH causes significant decrease in the spatial working memory. There was a significant reduction in the protein expression of Kalirin-7 in the hippocampus of hypoxia exposed rats (43.89 ± 7.43) as compared to the control (69.54 ± 10.99). The mRNA expression of Kalrin-7 also exhibits significant reduction (0.59 ± 0.05) in the exposed group as compared to the control (0.98 ± 0.07). Immunohistochemistry showed that Kalirin-7 is decreased significantly in CA1, CA3 and DG regions of the hippocampus. Moreover, memory deficits are significantly correlated with decreased immunoreactivity of the hippocampal Kalirin-7. In conclusion, it can be said therefore, that change in Kalirin-7 expression in the hippocampus is associated with HH induced working memory deficit.

摘要

低气压缺氧(HH)是在高海拔地区遇到的环境应激。已经表明,HH 导致脊柱萎缩和工作记忆缺陷。Kalirin-7 是一种突触后密度蛋白,在调节脊柱动力学及其可塑性方面起着重要和关键的作用。脊柱萎缩与 HH 引起的记忆缺陷有关,但 Kalirin-7 在这种现象中的作用尚未研究。因此,本研究旨在探讨慢性 HH 暴露对海马 Kalirin-7 表达的影响及其在空间工作记忆缺陷中的作用。成年大鼠(n = 12,3 个月龄)暴露于模拟海拔 25000 英尺的环境中 7 天。HH 暴露后,用放射臂迷宫和 T 迷宫评估空间工作记忆。海马 Kalrin-7 的表达在 mRNA 和蛋白水平上进行估计。行为实验的结果表明,HH 导致空间工作记忆显著下降。与对照组(69.54 ± 10.99)相比,缺氧暴露大鼠海马 Kalirin-7 的蛋白表达显著降低(43.89 ± 7.43)。暴露组 Kalrin-7 的 mRNA 表达也显著降低(0.59 ± 0.05)与对照组(0.98 ± 0.07)相比。免疫组织化学显示,海马 CA1、CA3 和 DG 区的 Kalirin-7 明显减少。此外,记忆缺陷与海马 Kalirin-7 免疫反应性降低显著相关。总之,可以说,海马 Kalirin-7 表达的变化与 HH 诱导的工作记忆缺陷有关。

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