Abstract：
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.
摘要：
限制性和重复行为（RRB）是各种神经精神疾病的特征之一，具有复杂多样的分子机制。重复的自我修饰行为是RRB在人类和啮齿动物中的表现之一。对重复自我修饰行为的神经机制的研究有望揭示RRB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）表现出显著增加的自我修饰，这表明Pax2基因参与了自我修饰行为的控制，但分子机制尚不清楚。在这项研究中,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，Nestin-Pax2小鼠的前额叶皮质（PFC）中神经递质系统存在兴奋性/抑制性失衡，Arc基因明显上调。这项研究表明，Pax2基因缺失小鼠重复自我修饰行为增加的潜在调控机制是Pax2基因的缺失影响PFC中Arc的表达，导致突触可塑性受损和兴奋性/抑制性失衡，并参与重复自我修饰行为的发生。
