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神经递素及其受体:BDNF 在 GABA 能神经发育和疾病中的作用。

Neurotrophins and Their Receptors: BDNF's Role in GABAergic Neurodevelopment and Disease.

机构信息

Instituto de Neurociencias de Castilla y León (INCyL), 37007 Salamanca, Spain.

Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.

出版信息

Int J Mol Sci. 2024 Jul 30;25(15):8312. doi: 10.3390/ijms25158312.

Abstract

Neurotrophins and their receptors are distinctly expressed during brain development and play crucial roles in the formation, survival, and function of neurons in the nervous system. Among these molecules, brain-derived neurotrophic factor (BDNF) has garnered significant attention due to its involvement in regulating GABAergic system development and function. In this review, we summarize and compare the expression patterns and roles of neurotrophins and their receptors in both the developing and adult brains of rodents, macaques, and humans. Then, we focus on the implications of BDNF in the development and function of GABAergic neurons from the cortex and the striatum, as both the presence of BDNF single nucleotide polymorphisms and disruptions in BDNF levels alter the excitatory/inhibitory balance in the brain. This imbalance has different implications in the pathogenesis of neurodevelopmental diseases like autism spectrum disorder (ASD), Rett syndrome (RTT), and schizophrenia (SCZ). Altogether, evidence shows that neurotrophins, especially BDNF, are essential for the development, maintenance, and function of the brain, and disruptions in their expression or signaling are common mechanisms in the pathophysiology of brain diseases.

摘要

神经营养因子及其受体在大脑发育过程中特异性表达,对神经系统中神经元的形成、存活和功能起关键作用。在这些分子中,脑源性神经营养因子(BDNF)因其参与调节 GABA 能系统的发育和功能而受到广泛关注。在这篇综述中,我们总结和比较了神经营养因子及其受体在啮齿动物、猕猴和人类发育中和成年脑中的表达模式和作用。然后,我们重点关注 BDNF 在皮质和纹状体 GABA 能神经元发育和功能中的作用,因为 BDNF 单核苷酸多态性的存在和 BDNF 水平的破坏会改变大脑中的兴奋/抑制平衡。这种失衡在神经发育疾病(如自闭症谱系障碍(ASD)、雷特综合征(RTT)和精神分裂症(SCZ))的发病机制中有不同的意义。总之,有证据表明,神经营养因子,尤其是 BDNF,对大脑的发育、维持和功能至关重要,其表达或信号转导的紊乱是大脑疾病病理生理学中的常见机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11311851/5a1b2d49966b/ijms-25-08312-g001.jpg

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