Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models
Name
nihms-1534970.pdf
Description
Accepted version
Size
3.29 MB
Format
Adobe PDF
Checksum (MD5)
dbe04807c2fc9c532ab389e72a593b14
Author(s)
Wells, Michael
Feng, Guoping
Date Issued
August 2019
Journal
Cell
Publisher
Elsevier BV
Citation
Orefice, Lauren L. et al. “Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.” Cell, 178, 4 (August 2019): 867–886.e24 © 2019 The Author(s)
Version
Author's final manuscript
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 GABAA 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. Treatment with a peripherally restricted GABAA receptor agonist in multiple distinct autism spectrum disorder mouse models reveals a potential therapeutic strategy for select ASD-related behaviors.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2019.07.024
