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  3. The effect of modulation Piezo2 by IGF-1 on tactile hypersensitivity in BTBR model mice

The effect of modulation Piezo2 by IGF-1 on tactile hypersensitivity in BTBR model mice

  • Life Sci. 2025 Mar 1:364:123449. doi: 10.1016/j.lfs.2025.123449.
Jinhe Zhai 1,  Haiying Hao 1,  Zihan Xu 1,  Akemi Tomoda 2,  Xinyi Zhang 1,  Xinxin Wang 1,  Yutong Liu 1,  Xuan Cao 1,  Dongxin Li 1,  Yuying Zhang 1,  Xueke Yao 1,  Lili Fan 3,  Jia Wang 4
Affiliations

Affiliations

  • 1 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin 150081, China; Heilongjiang Province Key Laboratory of Child Development and Genetic Research, Harbin Medical University, Harbin 150081, China.
  • 2 Research Center for Child Mental Development, University of Fukui, Fukui, Japan.
  • 3 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin 150081, China; Heilongjiang Province Key Laboratory of Child Development and Genetic Research, Harbin Medical University, Harbin 150081, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang 150081, China. Electronic address: 102337@hrbmu.edu.cn.
  • 4 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin 150081, China; Heilongjiang Province Key Laboratory of Child Development and Genetic Research, Harbin Medical University, Harbin 150081, China; Heilongjiang Academy of Medical Sciences, Harbin 150081, China; Research Center for Child Mental Development, University of Fukui, Fukui, Japan; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang 150081, China. Electronic address: 200231@hrbmu.edu.cn.
PMID: 39920984 DOI: 10.1016/j.lfs.2025.123449
Abstract

Aims: Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder. Individuals with ASD exhibit a higher incidence of tactile hypersensitivity. However, the underlying mechanisms remain unclear. The dorsal root ganglion (DRG) plays a crucial role in influencing tactile processing. This study aims to integrate RNA Sequencing (RNA-seq) and Molecular Biology experiments to identify key molecules involved in tactile hypersensitivity in ASD, further investigate related mechanisms, and develop effective intervention strategy.

Main methods: Using BTBR as the ASD model mouse and wild-type C57BL/6J as the control mouse, the differences in tactile sensitivity between them was compared. DRG were collected for RNA-seq analysis. Immunofluorescence and Enzyme-linked immunosorbent assay (ELISA) techniques were employed to validate the identified key molecules. And combined western blot to investigate the associated regulatory pathways.

Key findings: BTBR mice exhibit tactile hypersensitivity, which are associated with the upregulation of IGF-1 in the DRG. IGF-1 regulates the expression of Piezo2 ion channels. Inhibition of the IGF-1/Piezo2 pathway can significantly alleviate tactile hypersensitivity and social deficits in BTBR mice. Additionally, gentle touch intervention has been shown to reduce the overexpression of IGF-1/Piezo2 in the DRG, thereby ameliorating ASD symptoms.

Significance: The upregulation of the IGF-1/Piezo2 pathway in DRG may serve as a potential mechanism for tactile hypersensitivity observed in BTBR mice. Restoring the normalization of the IGF-1/Piezo2 is crucial for alleviating tactile hypersensitivity and synergistically rescues social deficits. Gentle touch intervention has the potential to ameliorate these behaviors through regulating IGF-1/Piezo2, positioning it as a promising strategy for ASD.

Keywords

Autism Spectrum Disorder; DRG; IGF-1; Piezo2; Social; Tactile; brain.

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