瑞士巴塞尔大学Peter Scheiffele小组在自闭症小鼠模型中实现催产素反应和社交行为的恢复。这一研究成果于2020年8月5日在线发表在《自然》上。
Title: Rescue of oxytocin response and social behaviour in a mouse model of autism
Author: Hanna Hrnberg, Enrique Prez-Garci, Dietmar Schreiner, Laetitia Hatstatt-Burkl, Fulvio Magara, Stephane Baudouin, Alex Matter, Kassoum Nacro, Eline Pecho-Vrieseling, Peter Scheiffele
Issue&Volume: 2020-08-05
Abstract: A fundamental challenge in developing treatments for autism spectrum disorders is the heterogeneity of the condition. More than one hundred genetic mutations confer high risk for autism, with each individual mutation accounting for only a small fraction of cases1,2,3. Subsets of risk genes can be grouped into functionally related pathways, most prominently those involving synaptic proteins, translational regulation, and chromatin modifications. To attempt to minimize this genetic complexity, recent therapeutic strategies have focused on the neuropeptides oxytocin and vasopressin4,5,6, which regulate aspects of social behaviour in mammals7. However, it is unclear whether genetic risk factors predispose individuals to autism as a result of modifications to oxytocinergic signalling. Here we report that an autism-associated mutation in the synaptic adhesion molecule Nlgn3 results in impaired oxytocin signalling in dopaminergic neurons and in altered behavioural responses to social novelty tests in mice. Notably, loss of Nlgn3 is accompanied by a disruption of translation homeostasis in the ventral tegmental area. Treatment of Nlgn3-knockout mice with a new, highly specific, brain-penetrant inhibitor of MAP kinase-interacting kinases resets the translation of mRNA and restores oxytocin signalling and social novelty responses. Thus, this work identifies a convergence between the genetic autism risk factor Nlgn3, regulation of translation, and oxytocinergic signalling. Focusing on such common core plasticity elements might provide a pragmatic approach to overcoming the heterogeneity of autism. Ultimately, this would enable mechanism-based stratification of patient populations to increase the success of therapeutic interventions.
DOI: 10.1038/s41586-020-2563-7
Source: https://www.nature.com/articles/s41586-020-2563-7
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html