ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1602201
Peripheral gene dysregulation in Negr1-deficient mice: Insights into possible links with affective behavior
Provisionally accepted
- Chungnam National University, Daejeon, Republic of Korea
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Neuronal growth regulator 1 (NEGR1) is a brain-enriched membrane protein that is also mildly expressed in peripheral tissues, including adipose tissue and skeletal muscle. Recent genome-wide analyses have identified NEGR1 as a risk factor for several human diseases, such as obesity, autism, and depression. However, its molecular function in these diseases remains unclear. To investigate the underlying mechanisms, particularly in peripheral-to-brain communication, we analyzed differentially expressed genes in four tissues (intestine, skeletal muscle, liver, and epididymal white adipose tissue) of Negr1 knockout mice and performed Gene Ontology (GO) enrichment analyses to identify the most related molecular pathway and core genes. The depressive-like behaviors observed in Negr1 -/-mice could be linked to dysregulated ion channels and transporters, leading to AP-1-involved inflammatory responses in peripheral tissues. In addition, interleukin (IL)-17 could be implicated in mediating the systematic inflammatory response in Negr1 -/-mice. This analysis provides insights into the function of NEGR1 in peripheral cells, as well as peripheral factors contributing to the peripheral-central immune crosstalk underlying human psychiatric disorders.
Keywords: Neuronal growth regulator 1, Obesity, Depression, Differentially expressed genes, Interleukin-17
Received: 01 Apr 2025; Accepted: 19 Jun 2025.
Copyright: © 2025 Lee, Maigoro, Yoo and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Soojin Lee, Chungnam National University, Daejeon, Republic of Korea
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