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脑源性神经营养因子(BDNF)对动物精神分裂症模型的影响。

Effects of brain-derived neurotrophic factor (BDNF) on the Schizophrenia model of animals.

作者信息

Shi Xiao-Jie, Du Yang, Li Xue-Song, Yao Ci-Qin, Cheng Yong

机构信息

Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, China.

Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, China.

出版信息

J Psychiatr Res. 2022 Dec;156:538-546. doi: 10.1016/j.jpsychires.2022.10.022. Epub 2022 Oct 13.

Abstract

BACKGROUND

Schizophrenia(SCZ)is a common clinically chronic psychiatric disease, and there have no effective specific therapeutic drugs in clinical practice currently. Studies have shown that the expression level of brain-derived neurotrophic factor (BDNF) in schizophrenics has decreased, so the expression level of BDNF has always been one of the evaluation indicators of SCZ. The neurotrophic factor hypothesis believes that increase or decrease of the expression level of BDNF may be one of the pathophysiological basis of SCZ.

METHODS

In this study, schizophrenic mice model with MK-801-induced glutamate dysfunction was established, and two doses of BDNF were administered to schizophrenic mice by intranasal administration. The four groups of mice: Control group, Model group, BDNF-20, BDNF-100 performed a series of behavioral tests to explore the effects of BDNF on sensory motor gating, anxiety, depression, social interaction, spontaneous activity, and memory in schizophrenic mice. Transcriptome sequencing of the BDNF high group and Model group in prefrontal cortex and hippocampus, using Metascape for gene function annotation and enrichment pathway analysis, to obtain BDNF transcription regulation information, understand the molecular mechanism of BDNF in SCZ further. Subsequently,immunofluorescence detected the effects of BDNF on neurons and glial cells in the prefrontal cortex and hippocampus.

CONCLUSION

The results show that BDNF can improve the behavior of SCZ by regulating the construction of the nervous system, affecting the growth and distribution of neurons and glial cells, and changing inflammation and apoptosis in the brain.

摘要

背景

精神分裂症(SCZ)是一种常见的临床慢性精神疾病,目前临床实践中尚无有效的特异性治疗药物。研究表明,精神分裂症患者脑源性神经营养因子(BDNF)的表达水平降低,因此BDNF的表达水平一直是SCZ的评估指标之一。神经营养因子假说认为,BDNF表达水平的升高或降低可能是SCZ病理生理基础之一。

方法

本研究建立了MK-801诱导谷氨酸功能障碍的精神分裂症小鼠模型,并通过鼻腔给药对精神分裂症小鼠给予两种剂量的BDNF。四组小鼠:对照组、模型组、BDNF-20、BDNF-100进行了一系列行为测试,以探讨BDNF对精神分裂症小鼠感觉运动门控、焦虑、抑郁、社交互动、自发活动和记忆的影响。对前额叶皮质和海马体中BDNF高表达组和模型组进行转录组测序,使用Metascape进行基因功能注释和富集通路分析,以获得BDNF转录调控信息,进一步了解BDNF在SCZ中的分子机制。随后,免疫荧光检测BDNF对前额叶皮质和海马体中神经元和神经胶质细胞的影响。

结论

结果表明,BDNF可通过调节神经系统的构建、影响神经元和神经胶质细胞的生长与分布以及改变大脑中的炎症和细胞凋亡来改善SCZ的行为。

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