Aerobic Exercise Improves Methamphetamine-Induced Olfactory Dysfunction Through α-Synuclein Intervention in Male Mice.
Aerobic Exercise Improves Methamphetamine-Induced Olfactory Dysfunction Through α-Synuclein Intervention in Male Mice.
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有氧运动通过α-突触核蛋白干预改善甲基苯丙胺诱导的雄性小鼠嗅觉功能障碍。
DOI：
10.3389/fnmol.2022.884790
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发表时间：
2022
影响因子：
4.8
通讯作者：
Qiu, Pingming
中科院分区：
文献类型：
--
作者：
Wang, Zhuo;Zheng, Rui;Wang, Xiaohan;Huang, Xuekun;Huang, Jian;Gu, Cihang;He, Yitong;Wu, Shuo;Chen, Jingyuan;Yang, Qintai;Qiu, Pingming
甲基苯丙胺（冰毒）是一种主要滥用的神经兴奋剂，其滥用通常与多种神经系统症状有关。嗅觉是一种高度依赖神经传递的生理过程；然而，甲基苯丙胺对嗅觉功能的影响及其潜在机制在很大程度上仍然未知。本研究旨在探讨甲基苯丙胺滥用对嗅觉系统的影响及其可能的机制。雄性小鼠连续4周每天服用冰毒诱导慢性冰毒滥用，然后系统地检测嗅觉表现。行为测试发现，服用冰毒的动物嗅觉阈值增加，嗅觉敏感性下降，嗅觉依赖的辨别能力下降，寻找埋藏食物的困难。值得注意的是，嗅球中α-突触核蛋白（α-syn）的沉积增加。腺相关病毒（Adeno-associated virus， AAV）介导的嗅球α-syn干预治疗可显著缓解冰毒诱导的嗅功能损伤，8周有氧运动通过相同的α-syn干预原理也有类似的效果。值得注意的是，运动介导的α-syn的减少抑制了异常放电活动，恢复了嗅球二尖瓣细胞的抑制性突触调节。这些发现提示α-syn参与了冰毒诱导的嗅觉功能障碍的致病机制，并为有氧运动治疗冰毒诱导的嗅觉功能障碍提供了可能的应用。
Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction.
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影响因子：
2.9
作者：
Jang, Yongchul;Koo, Jung-Hoon;Cho, Joon-Yong
通讯作者：
Cho, Joon-Yong
DOI：
10.1196/annals.1369.019
发表时间：
2006-01-01
期刊：
CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES
影响因子：
--
作者：
Mauceli, Giuseppe;Busceti, Carla I.;Fornai, Francesco
通讯作者：
Fornai, Francesco
影响因子：
--
作者：
Mahoney, James J., III;Hawkins, Rollin Y.;Newton, Thomas F.
通讯作者：
Newton, Thomas F.
影响因子：
3.7
作者：
Koo, Jung-Hoon;Cho, Joon-Yong
通讯作者：
Cho, Joon-Yong
影响因子：
5.3
作者：
El Hayek, Lauretta;Khalifeh, Mohamad;Sleiman, Sama F.
通讯作者：
Sleiman, Sama F.