Li Rui, Tang Jiaming, Wang Yizhuo, Wang Ying, Yang Hua, Wei Hongen
Department of Neurology, Shanxi Provincial People's Hospital, the Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030012, China; Shanxi Key Laboratory of Brain Disease Control, Shanxi Provincial People's Hospital, Taiyuan 030012, China.
School of the Third Clinic, Shanxi University of Chinese Medicine, Taiyuan 030024, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jan 10;128:110858. doi: 10.1016/j.pnpbp.2023.110858. Epub 2023 Sep 1.
Restricted and repetitive behaviors (RRBs) are one of the characteristics of various neuropsychiatric disorders with complex and diverse molecular mechanisms. Repetitive self-grooming behavior is one of the manifestations of RRBs in humans and rodents. Research on the neural mechanism of repetitive self-grooming behavior is expected to reveal the underlying logic of the occurrence of RRBs. Pax2 is an important member of the paired-box transcription factor family. It is expressed in different regions of the developing central nervous system. Our previous study showed that Pax2 heterozygous gene knockout mice (Pax2 KO mice) exhibit significantly increased self-grooming, which suggests that the Pax2 gene is involved in the control of self-grooming behavior, but the molecular mechanism is still unclear. In this study, we further constructed the Pax2 neuron-specific deletion mice (Nestin-Pax2 mice). Targeted metabolomics and transcriptomics techniques was used to analyze. The results showed that there is an excitatory/inhibitory imbalance of the neurotransmitter system and the Arc gene was significantly up-regulated in the prefrontal cortex (PFC) of Nestin-Pax2 mice. This study suggests that the potential regulatory mechanism of the increased repetitive self-grooming behavior in Pax2 gene deletion mice is that the deletion of the Pax2 gene affects the expression of Arc in the PFC, leading to impaired synaptic plasticity and excitatory/inhibitory imbalance, and participating in the occurrence of repetitive self-grooming behavior.
受限和重复行为（RRBs）是多种神经精神疾病的特征之一，其分子机制复杂多样。重复自我梳理行为是人类和啮齿动物RRBs的表现之一。对重复自我梳理行为神经机制的研究有望揭示RRBs发生的潜在逻辑。Pax2是配对盒转录因子家族的重要成员。它在发育中的中枢神经系统的不同区域表达。我们之前的研究表明，Pax2杂合基因敲除小鼠（Pax2 KO小鼠）的自我梳理行为显著增加，这表明Pax2基因参与了自我梳理行为的控制，但其分子机制仍不清楚。在本研究中，我们进一步构建了Pax2神经元特异性缺失小鼠（Nestin-Pax2小鼠）。使用靶向代谢组学和转录组学技术进行分析。结果表明，神经递质系统存在兴奋/抑制失衡，且Nestin-Pax2小鼠前额叶皮质（PFC）中的Arc基因显著上调。本研究表明，Pax2基因缺失小鼠重复自我梳理行为增加的潜在调节机制是，Pax2基因的缺失影响了PFC中Arc的表达，导致突触可塑性受损和兴奋/抑制失衡，并参与了重复自我梳理行为的发生。
