دورية أكاديمية
SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice
| العنوان: | SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice |
|---|---|
| المؤلفون: | Xiang, Ludan, Wu, Qian, Sun, Huankun, Miao, Xuemeng, Lv, Zhaoting, Liu, Huitao, Chen, Lan, Gu, Yanrou, Chen, Jianjun, Zhou, Siyao, Jiang, Huixia, Du, Siyu, Zhou, Yixin, Dong, Hui, Fan, Yiren, Miao, Shuangda, Lu, Qi, Chang, Liyun, Wang, Hui, Lu, Yi, Xu, Xingxing, Wang, Wei, Huang, Zhihui |
| المساهمون: | National Natural Science Foundation of China, Xinmiao Talents Program of Zhejiang Province, China |
| المصدر: | Cell Death & Disease ; volume 13, issue 7 ; ISSN 2041-4889 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Cell Biology, Cellular and Molecular Neuroscience, Immunology |
| الوصف: | 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 (SARM1 PV -CKO) mice. SARM1 PV -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 SARM1 PV -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 SARM1 PV -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 SARM1 PV -CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41419-022-05083-2 |
| الإتاحة: | https://doi.org/10.1038/s41419-022-05083-2Test https://www.nature.com/articles/s41419-022-05083-2.pdfTest https://www.nature.com/articles/s41419-022-05083-2Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.7FEDB6CB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41419-022-05083-2 |
|---|