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血脑屏障功能障碍在重度抑郁症发病机制中的作用。

Blood-Brain Barrier Dysfunction in the Pathogenesis of Major Depressive Disorder.

机构信息

Department of Immunology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Department of Laboratory Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China.

出版信息

Cell Mol Neurobiol. 2022 Nov;42(8):2571-2591. doi: 10.1007/s10571-021-01153-9. Epub 2021 Oct 12.

Abstract

Major depression represents a complex and prevalent psychological disease that is characterized by persistent depressed mood, impaired cognitive function and complicated pathophysiological and neuroendocrine alterations. Despite the multifactorial etiology of depression, one of the most recent factors to be identified as playing a critical role in the development of depression is blood-brain barrier (BBB) disruption. The occurrence of BBB integrity disruption contributes to the disturbance of brain homeostasis and leads to complications of neurological diseases, such as stroke, chronic neurodegenerative disorders, neuroinflammatory disorders. Recently, BBB associated tight junction disruption has been shown to implicate in the pathophysiology of depression and contribute to increased susceptibility to depression. However, the underlying mechanisms and importance of BBB damage in depression remains largely unknown. This review highlights how BBB disruption regulates the depression process and the possible molecular mechanisms involved in development of depression-induced BBB dysfunction. Moreover, insight on promising therapeutic targets for treatment of depression with associated BBB dysfunctions are also discussed.

摘要

重度抑郁症是一种复杂且常见的心理疾病,其特征为持续的抑郁情绪、认知功能受损以及复杂的病理生理和神经内分泌改变。尽管抑郁症的病因是多因素的,但最近发现的一个在抑郁症发展中起关键作用的因素是血脑屏障(BBB)的破坏。BBB 完整性的破坏会导致脑内环境稳态的紊乱,并导致中风、慢性神经退行性疾病、神经炎性疾病等神经系统疾病的并发症。最近,研究表明 BBB 相关紧密连接的破坏与抑郁症的病理生理学有关,并导致对抑郁症的易感性增加。然而,BBB 损伤在抑郁症中的潜在机制和重要性在很大程度上仍然未知。本综述强调了 BBB 破坏如何调节抑郁症的发生过程,以及涉及抑郁症引起的 BBB 功能障碍的可能分子机制。此外,还讨论了针对与 BBB 功能障碍相关的抑郁症的有前途的治疗靶点。

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