Zhao Ming, Cheng Xiang, Lin Xiao, Han Ying, Zhou Yanzhao, Zhao Tong, He Yunling, Wu Liying, Zhao Yongqi, Fan Ming, Zhu Lingling
Institute of Military Cognition and Brain Sciences, Beijing, China.
Institute of Military Cognition and Brain Sciences, Beijing, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
Behav Brain Res. 2019 May 2;363:30-37. doi: 10.1016/j.bbr.2019.01.048. Epub 2019 Jan 28.
Metformin, an antidiabetic biguanide, reduces hyperglycemia by improving glucose utilization and reducing gluconeogenesis. Recently, an increasing number of studies have shown that metformin also led to a significant clinical improvement in memory and cognition in different clinical settings. In the present study, we investigated whether metformin administration protects against memory impairment and neuron damage caused by acute exposure to hypobaric hypoxia and screened the possible molecular mechanisms with a focused gene array. We found that metformin treatment obviously attenuated spatial memory and recognition memory impairment resulting from acute hypobaric hypoxia exposure but had no effect on general locomotor and behavioral activity. Moreover, the results of Nissl and TUNEL staining showed that neuron damage and cell apoptosis caused by hypobaric hypoxia exposure was also inhibited by metformin pretreatment. At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia. These data suggested that metformin pretreatment is a feasible strategy for preventing memory impairment under hypobaric hypoxia.
二甲双胍是一种抗糖尿病双胍类药物，通过改善葡萄糖利用和减少糖异生来降低高血糖。最近，越来越多的研究表明，二甲双胍在不同临床环境中也能显著改善记忆和认知功能。在本研究中，我们调查了给予二甲双胍是否能预防急性低压缺氧所致的记忆障碍和神经元损伤，并通过聚焦基因芯片筛选了可能的分子机制。我们发现，二甲双胍治疗明显减轻了急性低压缺氧暴露所致的空间记忆和识别记忆障碍，但对一般运动和行为活动没有影响。此外，尼氏染色和TUNEL染色结果显示，二甲双胍预处理也抑制了低压缺氧暴露所致的神经元损伤和细胞凋亡。在分子水平上，我们发现二甲双胍预处理不仅在mRNA和蛋白质水平上阻止了FOS、JUNB和BDNF的变化，而且在暴露于低压缺氧后还增加了突触后支架基因HOMER和PSD95的表达。这些数据表明，二甲双胍预处理是预防低压缺氧下记忆障碍的一种可行策略。
