Metabolomics and transcriptomics analysis of prefrontal cortex in the Pax2 neuron-specific deletion mice

Rui Li; Jiaming Tang; Yizhuo Wang; Ying Wang; Hua Yang; Hongen Wei

doi:10.1016/j.pnpbp.2023.110858

Metabolomics and transcriptomics analysis of prefrontal cortex in the Pax2 neuron-specific deletion mice

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jan 10:128:110858. doi: 10.1016/j.pnpbp.2023.110858. Epub 2023 Sep 1.

Authors

Rui Li¹, Jiaming Tang², Yizhuo Wang³, Ying Wang³, Hua Yang⁴, Hongen Wei⁵

Affiliations

¹ 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.
² School of the Third Clinic, Shanxi University of Chinese Medicine, Taiyuan 030024, China.
³ Department of Neurology, Shanxi Provincial People's Hospital, the Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030012, China.
⁴ 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. Electronic address: gnayhua@163.com.
⁵ 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. Electronic address: hongen.wei@sxmu.edu.cn.

PMID: 37660748
DOI: 10.1016/j.pnpbp.2023.110858

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.

Keywords: Pax2; Prefrontal cortex; Restricted and repetitive behaviors; Targeted metabolomics; Transcriptomics.