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脑源性神经营养因子(BDNF)与慢性精神分裂症中氧化应激之间的相互作用。

The interplay between BDNF and oxidative stress in chronic schizophrenia.

作者信息

Zhang Xiang Yang, Chen Da-Chun, Tan Yun-Long, Tan Shu-Ping, Wang Zhi-Ren, Yang Fu-De, Okusaga Olaoluwa O, Zunta-Soares Giovana B, Soares Jair C

机构信息

Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Department of Psychiatry and Behavioral Sciences, Harris County Psychiatric Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Beijing HuiLongGuan Hospital, Peking University, Beijing, China.

出版信息

Psychoneuroendocrinology. 2015 Jan;51:201-8. doi: 10.1016/j.psyneuen.2014.09.029. Epub 2014 Oct 7.

Abstract

Neurodegenerative processes may be involved in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin and oxidative stress (OS) may be critical for several pathological manifestations of neurodegenerative disorders. Accumulating evidence suggests that both BDNF and OS may be involved in the pathophysiology of schizophrenia. However, the possible interaction between BDNF and OS has been under-investigated. Serum BDNF, plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 164 chronic medicated schizophrenia and 50 healthy controls. Schizophrenic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive and depressive factors derived from the five factor model of the PANSS. Compared to the control group, the patients exhibited a significant decrease in BDNF levels, in the activities of SOD and GSH-Px but a significant increase in MDA levels. In patients, but not in controls, we observed a significant negative correlation between BDNF and SOD. Furthermore, the interaction between BDNF and CAT was associated with the PANSS cognitive factor, and the interaction between BDNF and GSH-Px with the PANSS depressive factor. Both decreased BDNF levels and OS may be implicated in the pathophysiology of chronic schizophrenia. Their inverse association only in the schizophrenia group may reflect a pathological mechanism involving an interaction of oxidative damage and neurotrophin dysfunction. Moreover, OS may interact with the BDNF system to influence the clinical symptoms and cognitive impairment in schizophrenia, which is line with the neurodevelopmental hypothesis of schizophrenia.

摘要

神经退行性过程可能参与了精神分裂症的发病机制。脑源性神经营养因子(BDNF)是分布最广泛的神经营养蛋白,而氧化应激(OS)可能对神经退行性疾病的几种病理表现至关重要。越来越多的证据表明,BDNF和OS都可能参与精神分裂症的病理生理学过程。然而,BDNF与OS之间可能的相互作用尚未得到充分研究。我们采用既定方法分析了164例慢性服药的精神分裂症患者和50名健康对照者的血清BDNF、血浆丙二醛(MDA)水平以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性。采用阳性和阴性症状量表(PANSS)评估精神分裂症症状,并从PANSS的五因素模型中得出认知和抑郁因子。与对照组相比,患者的BDNF水平、SOD和GSH-Px活性显著降低,但MDA水平显著升高。在患者中,而非对照组中,我们观察到BDNF与SOD之间存在显著的负相关。此外,BDNF与CAT之间的相互作用与PANSS认知因子相关,BDNF与GSH-Px之间的相互作用与PANSS抑郁因子相关。BDNF水平降低和OS可能都与慢性精神分裂症的病理生理学有关。它们仅在精神分裂症组中的负相关可能反映了一种涉及氧化损伤和神经营养因子功能障碍相互作用的病理机制。此外,OS可能与BDNF系统相互作用,影响精神分裂症的临床症状和认知障碍,这与精神分裂症的神经发育假说一致。

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