2. Academic Validation
  3. Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

  • Life Sci. 2025 Sep 15:377:123797. doi: 10.1016/j.lfs.2025.123797.
Feng Wang 1,  Zehui Liu 2,  Jingyi Hu 1,  Zeyu Cheng 1,  Shidan Liu 1,  Wenru Tian 1,  Yilin Zhang 1,  Lingyuan Yang 1,  Tianyu Liu 1,  Caihong Sun 3,  Mingyang Zou 4
Affiliations

Affiliations

  • 1 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, China; Heilongjiang Province Key Laboratory of Child Development and Genetic Research, Harbin Medical University, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang, China.
  • 2 Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, China.
  • 3 Department of Developmental Behavioral Pediatrics, the Sixth Affiliated Hospital of Harbin Medical University, China. Electronic address: 200033@hrbmu.edu.cn.
  • 4 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, China; Heilongjiang Province Key Laboratory of Child Development and Genetic Research, Harbin Medical University, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang, China. Electronic address: mingyangshine@hrbmu.edu.cn.
PMID: 40484367 DOI: 10.1016/j.lfs.2025.123797
Abstract

We previously found that enhancing the levels of 2-arachidonoylglycerol (2-AG) and anandamide (AEA) could improve autism spectrum disorder (ASD) symptoms. This study investigated the effect of cannabinoid type 1 receptor (CB1R) in ASD with pharmacological, genetic and brain-targeted intervention and the underlying mechanisms. Results showed that blocking CB1R counteracted the beneficial effects of boosting 2-AG or AEA on ASD-like behaviors in valproic acid (VPA)-exposed mice. Besides, CB1R knockout mice exhibited ASD-like behaviors and synaptic deficits. In CB1R-specific brain-targeted regulation, activating CB1R ameliorated synaptic dysfunction, including neuronal complexity, spine density, dendritic integrity, synaptic protein expression, and neuronal damage. Moreover, activating CB1R enhanced the expression and current density of Kir4.1, indicating that CB1R may influence synaptic activity by modulating Kir4.1. Collectively, our findings indicated a critical role for CB1R in the improvement of ASD-like behavior and synaptic dysfunction, which may offer promising avenues for developing effective treatments for ASD.

Keywords

Autism spectrum disorder; Brain-targeted; CB1R; Kir4.1; Synaptic function.

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