褪黑素抑制过度的线粒体自噬并改善卒中后认知障碍

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Abstract Objective This study aimed to investigate the protective effect and mechanism of melatonin (MT) in post-stroke cognitive impairment (PSCI). Methods Male C57BL/6J mice were randomly divided into Sham, Stroke, and Stroke+MT groups (n=7/group). Photothrombotic-induced stroke model mice were injected intraperitoneally with saline or MT (20 mg/kg) for 21 consecutive days after modeling. Behavioral tests were performed to examine the cognitive function of the mice, Nissl staining to detect neuronal damage, and Western blotting to detect apoptosis, synaptic plasticity and mitophagy. Results Compared with Sham mice, stroke mice showed a significantly reduction in the discrimination index in the novel object recognition test and the time spent in the novel arm of the Y maze. The number of neurons in the hippocampus and cortex were significantly reduced. The levels of proapoptotic proteins (Bax, cleaved Caspase-3) were upregulated, the levels of synapse-related proteins (PSD-95, Synaptophysin) were downregulated, and the levels of mitophagy-related proteins (PINK1, Parkin) were upregulated. MT significantly increased the discrimination index in the novel object recognition test and the time spent in the novel arm of the Y maze. The number of hippocampal and cortical neurons were significantly increased. The levels of proapoptotic proteins (Bax, cleaved Caspase-3) were downregulated, the levels of synapse-related proteins (PSD-95, Synaptophysin) were upregulated, and the levels of mitophagy-related proteins (PINK1, Parkin) were downregulated. Conclusion MT inhibited excessive mitophagy and ameliorated PSCI.

Key words： post-stroke cognitive impairment mitophagy melatonin hippocampus apoptosis

Received: 01 March 2024

PACS:	R741
	R363

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	Articles by authors
	FANG Qian
	LI Yuqing
	LI Keqing
	DUAN Meiyu
	LAI Sisi
	TANG Zixing
	YUAN Shishan
	SHI Yan

Cite this article:

FANG Qian,LI Yuqing,LI Keqing等. Melatonin inhibits excessive mitophagy and improves cognitive impairment after stroke[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2024, 21(3): 22-27.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2024/V21/I3/22

[1] 郝曼均, 曹智鑫, 李光硕, 等. 英国国家卒中临床指南2023版要点及解读——缺血性卒中 [J]. 中国卒中杂志, 2023, 18(12): 1357-1364+1343.
[2] 崔倩, 李瑞玲, 栗文娟, 等. 《脑卒中后认知障碍》指南解读[J]. 护理研究, 2022, 36(22): 3949-3952.
[3] DAWSON T M, DAWSON V L.Mitochondrial Mechanisms of Neuronal Cell Death: Potential Therapeutics[J]. Annu Rev Pharmacol Toxicol, 2017, 57: 437-454.
[4] 卢靖, 张冬梅, 唐晓雷, 等. 抵当汤调节线粒体自噬对脑出血后神经损伤的保护作用及机制[J]. 中国老年学杂志, 2023, 43(22): 5541-5547.
[5] ALGHAMDI B S.The neuroprotective role of melatonin in neurological disorders[J]. J Neurosci Res, 2018, 96(7): 1136-1149.
[6] CAO R, LI L, ZHANG W, et al.Melatonin attenuates repeated mild traumatic brain injury-induced cognitive deficits by inhibiting astrocyte reactivation[J]. Biochem Biophys Res Commun, 2021, 580: 20-27.
[7] KNIERIM J J.The hippocampus[J]. Curr Biol, 2015, 25(23): R1116-1121.
[8] 李佳. 焦亡抑制剂Vx765对脑缺血后神经元损伤的影响及分子机制 [D]. 武汉: 华中科技大学, 2020.
[9] Benjamin E J, Blaha M J, Chiuve S E, et al.Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association[J]. Circulation, 2017, 135(10): e146-e603.
[10] 刘伟丽, 储芳, 郭万申, 等. 脑卒中康复患者睡眠质量现状及影响因素分析[J]. 湖南师范大学学报 (医学版), 2023, 20(04): 148-152.
[11] MIJAJLOVIĆ M D, PAVLOVIĆ A, BRAININ M, et al.Post-stroke dementia - a comprehensive review[J]. BMC Med, 2017, 15(1): 11.
[12] PANDI-PERUMAL S R, BAHAMMAM A S, BROWN G M, et al. Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes[J]. Neurotox Res, 2013, 23(3): 267-300.
[13] GANIE S A, DAR T A, BHAT A H, et al.Melatonin: A Potential Anti-Oxidant Therapeutic Agent for Mitochondrial Dysfunctions and Related Disorders[J]. Rejuvenation Res, 2016, 19(1): 21-40.
[14] SOMMER C J.Ischemic stroke: experimental models and reality[J]. Acta Neuropathol, 2017, 133(2): 245-261.
[15] ZHANG C, LI S, WANG Y, et al.Photochemically induced thalamus infarction impairs cognition in a mouse model[J]. Stroke Vasc Neurol, 2023, 8(6): 444-452.
[16] LISMAN J, BUZSÁKI G, EICHENBAUM H, et al. Viewpoints: how the hippocampus contributes to memory, navigation and cognition[J]. Nat Neurosci, 2017, 20(11): 1434-1447.
[17] 张芳, 刘建荣, 秦琴, 等. 基于PINK1/Parkin介导的线粒体自噬与细胞凋亡探讨伸曲助育汤改善精索静脉曲张大鼠生精功能的机制[J]. 中国中西医结合杂志, 2024, 44(02): 202-207.
[18] KAGEYAMA Y, HOSHIJIMA M, SEO K, et al.Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain[J]. Embo j, 2014, 33(23): 2798-2813.
[19] 史可鉴. 基于线粒体自噬PINK1/Parkin信号通路探讨逆灸对调控阿尔茨海默病大鼠认知功能障碍的机制研究 [D]. 合肥: 安徽中医大学, 2023.
[20] XIAO Q, LIU H, YANG C, et al.Bushen-Yizhi formula exerts neuroprotective effect via inhibiting excessive mitophagy in rats with chronic cerebral hypoperfusion[J]. J Ethnopharmacol, 2023, 310: 116326.
[21] REITER R J, ROSALES-CORRAL S, TAN D X, et al.Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas[J]. Cell Mol Life Sci, 2017, 74(21): 3863-3881.
[22] 郝广志, 初广新, 陈立刚, 等. 褪黑素协同丙戊酸钠减轻糖氧剥夺诱导的小鼠神经元损伤[J]. 神经解剖学杂志, 2022, 38(02): 209-213.
[23] ZHANG Y, CHEN D, WANG Y, et al.Neuroprotective effects of melatonin-mediated mitophagy through nucleotide-binding oligomerization domain and leucine-rich repeat-containing protein X1 in neonatal hypoxic-ischemic brain damage[J]. Faseb J, 2023, 37(2): e22784.
[24] BAI Y, YANG Y, GAO Y, et al.Melatonin postconditioning ameliorates anoxia/reoxygenation injury by regulating mitophagy and mitochondrial dynamics in a SIRT3-dependent manner[J]. Eur J Pharmacol, 2021, 904: 174157.