哈佛医学院David D. Ginty课题组取得一项新突破。他们研究出以外周机械感觉神经元为靶点，可以改善ASD模型中的触觉相关表型。相关论文于2019年8月8日发表在《细胞》杂志上。

研究组在不同的ASD小鼠模型中发现了不同的体感神经元病理生理学机制，这些机制构成了触觉异常的基础，并与一些ASD相关的行为有关。外周机械感觉神经元中ASD相关基因Shank3或Mecp2的发育丧失导致区域特异性脑异常，揭示了体感过度反应与异常行为发生之间的联系。此外，使用直接作用于机械感觉神经元的外周限制性GABA A受体激动剂的急性治疗，降低了六种不同ASD模型中的触觉过度反应。Mecp2和Shank3突变小鼠的慢性治疗改善了身体状况，如一些大脑异常，焦虑行为和一些社会障碍，但没有影响记忆障碍，运动缺陷。研究发现了一种通过靶向外周机械感觉神经元，用于治疗触觉过度反应和选择ASD相关行为的潜在治疗策略。

研究人员表示，躯体感觉过度反应在自闭症谱系障碍(ASDs)患者中很常见，并被认为是导致核心ASD行为的原因之一。然而，目前缺乏对过度反应和ASDs有效的治疗手段。

附：英文原文

Title: Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models

Author: Lauren L. Orefice, Jacqueline R. Mosko, Danielle T. Morency, Michael F. Wells, Aniqa Tasnim, Shawn M. Mozeika, Mengchen Ye, Anda M. Chirila, Alan J. Emanuel, Genelle Rankin, Ryann M. Fame, Maria K. Lehtinen, Guoping Feng, David D. Ginty

Issue&Volume: Volume 178 Issue 4

Abstract: Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors. Moreover, acute treatment with a peripherally restricted GABA A receptor agonist that acts directly on mechanosensory neurons reduced tactile over-reactivity in six distinct ASD models. Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, some brain abnormalities, anxiety-like behaviors, and some social impairments but not memory impairments, motor deficits, or overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.

DOI: https://doi.org/10.1016/j.cell.2019.07.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30791-3