2. Academic Validation
  3. SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice

SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice

  • Cell Death Dis. 2022 Jul 22;13(7):638. doi: 10.1038/s41419-022-05083-2.
Ludan Xiang  # 1 2,  Qian Wu  # 1,  Huankun Sun  # 1,  Xuemeng Miao 1,  Zhaoting Lv 1 2,  Huitao Liu 3,  Lan Chen 1 4,  Yanrou Gu 1,  Jianjun Chen 1,  Siyao Zhou 1,  Huixia Jiang 1,  Siyu Du 1,  Yixin Zhou 1,  Hui Dong 1,  Yiren Fan 1,  Shuangda Miao 1,  Qi Lu 1,  Liyun Chang 1,  Hui Wang 1,  Yi Lu 1,  Xingxing Xu 5,  Wei Wang 6 7 8,  Zhihui Huang 9 10 11
Affiliations

Affiliations

  • 1 School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 2 Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang, China.
  • 3 Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
  • 4 Department of Child Psychiatry, Shaoxing Seventh People's Hospital, Shaoxing, 312000, Zhejiang, China.
  • 5 School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 6 School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. wangwei@wmu.edu.cn.
  • 7 Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. wangwei@wmu.edu.cn.
  • 8 Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. wangwei@wmu.edu.cn.
  • 9 School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. huang0069@hznu.edu.cn.
  • 10 School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. huang0069@hznu.edu.cn.
  • 11 College of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China. huang0069@hznu.edu.cn.
  • # Contributed equally.
PMID: 35869039 DOI: 10.1038/s41419-022-05083-2
Abstract

Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1PV-CKO) mice. SARM1PV-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1PV-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to Apoptosis. Furthermore, the expression of c-Fos was shown to increase in SARM1PV-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA Receptor agonists in SARM1PV-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD.

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