State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology, School of Life Sciences, Nanjing University, Nanjing, China.
Institute for Brain Sciences, Nanjing University, Nanjing, China.
Cerebellum. 2023 Oct;22(5):888-904. doi: 10.1007/s12311-022-01466-5. Epub 2022 Aug 30.
The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.
经典的运动中枢小脑是自闭症谱系障碍(ASD)中最一致的异常结构之一,神经肽催产素越来越多地被探索作为 ASD 的潜在药物治疗方法。然而,催产素是否以小脑作为治疗靶点仍不清楚。在这里,我们报告催产素受体(OXTR)在小脑小叶 Crus I 的浦肯野细胞(PCs)中的定位,该定位与 ASD 相关的回路功能连接。OXTR 的激活既不影响正常 PCs 的放电活动、内在兴奋性和突触传递,也不能改善自闭症的母体免疫激活(MIA)小鼠模型中 PCs 的异常内在兴奋性和突触传递。此外,在野生型小鼠的 Crus I 中阻断 OXTR 不会诱导出类似自闭症的社交、刻板、认知和焦虑样行为。这些结果表明,Crus I PCs 中的催产素信号似乎与 ASD 病理生理学无关,并有助于理解催产素在 ASD 治疗中的靶点和机制。