Activation of cholinergic system partially rescues olfactory dysfunction-induced learning and memory deficit in mice
Activation of cholinergic system partially rescues olfactory dysfunction-induced learning and memory deficit in mice
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DOI：
10.1016/j.bbr.2021.113283
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发表时间：
2021-04
影响因子：
2.7
通讯作者：
Kohei Takahashi;M. Tsuji;O. Nakagawasai;S. Katsuyama;K. Miyagawa;K. Kurokawa;Atsumi Mochida-Saito
中科院分区：
文献类型：
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作者：
Kohei Takahashi;M. Tsuji;O. Nakagawasai;S. Katsuyama;K. Miyagawa;K. Kurokawa;Atsumi Mochida-Saito
嗅觉缺陷与神经退行性疾病如阿尔茨海默病有关。最近的一项研究报告，鼻腔硫酸锌（硫酸锌）治疗的小鼠表现出嗅觉和记忆缺陷。然而，嗅觉缺陷引起的学习记忆障碍是否与脑中的胆碱能系统有关仍不清楚。在这项研究中，我们评估了嗅觉功能的掩埋食物发现测试，学习和记忆功能的Y-迷宫和被动回避测试硫酸锌处理的小鼠。采用免疫印迹法检测嗅球、前额叶、海马和杏仁核胆碱乙酰转移酶（ChAT）蛋白的表达。此外，我们观察了乙酰胆碱酯酶抑制剂毒扁豆碱对硫酸锌诱导的学习记忆障碍的影响。我们发现，鼻内硫酸锌治疗的小鼠表现出嗅觉功能障碍，而这种变化在治疗后第14天恢复。短期和长期的学习和记忆受损的第4和第7天与硫酸锌治疗后，而前者，而不是后者，在治疗后第14天恢复。嗅觉功能和短期记忆之间存在显著相关性，但与长期记忆无关。硫酸锌处理后第4天降低了OB中的ChAT水平，第7天分别增加和降低了OB和海马中的ChAT水平。毒扁豆碱改善了硫酸锌诱导的短期记忆缺陷，但没有改善长期记忆。综上所述，本研究结果表明，短期记忆可能通过胆碱能系统与嗅觉功能密切相关。
Deficits in olfaction are associated with neurodegenerative disorders such as Alzheimer’s disease. A recent study reported that intranasal zinc sulfate (ZnSO4)-treated mice show olfaction and memory deficits. However, it remains unknown whether olfaction deficit-induced learning and memory impairment is associated with the cholinergic system in the brain. In this study, we evaluated olfactory function by the buried food find test, and learning and memory function by the Y-maze and passive avoidance tests in ZnSO4-treated mice. The expression of choline acetyltransferase (ChAT) protein in the olfactory bulb (OB), prefrontal cortex, hippocampus, and amygdala was assessed by western blotting. Moreover, we observed the effect of the acetylcholinesterase inhibitor physostigmine on ZnSO4-induced learning and memory deficits. We found that intranasal ZnSO4-treated mice exhibited olfactory dysfunction, while this change was recovered on day 14 after treatment. Both short-term and long-term learning and memory were impaired on days 4 and 7 after treatment with ZnSO4, whereas the former, but not the latter, was recovered on day 14 after treatment. A significant correlation was observed between olfactory function and short-term memory, but not long-term memory. Treatment with ZnSO4decreased the ChAT level in the OB on day 4, and increased and decreased the ChAT levels in the OB and hippocampus on day 7, respectively. Physostigmine improved the ZnSO4-induced deficit in short-term, but not long-term, memory. Taken together, the present results suggest that short-term memory may be closely associated with olfactory function via the cholinergic system.