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前额皮质中的脑源性神经营养因子(BDNF)增强了自闭症 BTBR 小鼠模型的社交兴趣。

Brain-Derived Neurotrophic Factor (BDNF) in the Frontal Cortex Enhances Social Interest in the BTBR Mouse Model of Autism.

机构信息

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.

出版信息

Biochemistry (Mosc). 2024 Aug;89(8):1509-1518. doi: 10.1134/S0006297924080091.

Abstract

A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals.

摘要

大量证据表明脑源性神经营养因子(BDNF)参与了自闭症谱系障碍(ASD)的发病机制。许多研究都指出,BTBR 小鼠(自闭症模型)的海马体和额叶皮质中 BDNF 含量不足。早些时候,我们发现诱导 BTBR 小鼠海马体中的 BDNF 过表达可降低焦虑和刻板行为的严重程度,但不影响社交兴趣。在这里,我们使用腺相关病毒载体在 BTBR 小鼠的额叶皮质神经元中诱导 BDNF 过表达,这导致在三箱社交测试中社交兴趣显著增加。同时,刻板行为、探索行为、焦虑样行为和新物体识别不受影响。因此,我们首次表明,额叶皮质中 BDNF 的存在对于 BTBR 小鼠社交兴趣的表达至关重要,因为补偿该结构中的不足消除了这些动物社交行为中自闭症样缺陷。

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