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DHF-7 ameliorates behavioral disorders and white matter lesions by regulating BDNF and Fyn in a mouse model of schizophrenia induced by cuprizone and MK-801.

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机构: [1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China [2]National Center for Neurological Disorders, Beijing, China [3]National Clinical Research Center for Geriatric Diseases, Beijing, China [4]Beijing Institute for Brain Disorders, Beijing, China [5]Beijing Engineering Research Center for Nerve System Drugs, Beijing, China [6]Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China. [7]Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan, 450003, China.
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关键词: Dihydrofavanone schizophrenia cognitive impairment white matter lesion brain-derived neurotrophic factor Fyn

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Schizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801.After intragastric administration of DHF-7 for seven weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins.The results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated Fyn, thus activating the TrkB/Fyn/NMDAR2B and Raf/MEK/ERK signaling pathways.Our results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.

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出版当年[2021]版:
大类 | 2 区 医学
小类 | 2 区 临床神经病学 2 区 神经科学 2 区 药学 2 区 精神病学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 临床神经病学 3 区 神经科学 3 区 精神病学
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出版当年[2020]版:
Q1 CLINICAL NEUROLOGY Q1 PSYCHIATRY Q1 PHARMACOLOGY & PHARMACY Q2 NEUROSCIENCES
最新[2023]版:
Q1 CLINICAL NEUROLOGY Q1 PSYCHIATRY Q1 NEUROSCIENCES Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China [2]National Center for Neurological Disorders, Beijing, China [3]National Clinical Research Center for Geriatric Diseases, Beijing, China [4]Beijing Institute for Brain Disorders, Beijing, China [5]Beijing Engineering Research Center for Nerve System Drugs, Beijing, China [6]Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China. [7]Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan, 450003, China.
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通讯作者:
通讯机构: [1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China [2]National Center for Neurological Disorders, Beijing, China [3]National Clinical Research Center for Geriatric Diseases, Beijing, China [4]Beijing Institute for Brain Disorders, Beijing, China [5]Beijing Engineering Research Center for Nerve System Drugs, Beijing, China [6]Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China. [*1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, 45 Chang-chun Street, Beijing 100053, China
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