Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models
Author(s)Wells, Michael; Feng, Guoping
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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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MIT
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)
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