Journal
CELL
Volume 178, Issue 4, Pages 867-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.07.024
Keywords
-
Categories
Funding
- Harvard Research Instrumentation Core for help with electrophysiology and behavioral assay development (Core Grant for Vision Research) [EY012196]
- Goldenson Postdoctoral Fellowship
- SFARI Research Award from the Simons Foundation
- Harvard Blavatnik Accelerator and QFASTR
- Edward R. and Anne G. Lefler Center for Neurodegenerative Disorders
- New York Stem Cell Foundation
- Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT
- NIH [K99 NS101057, F31 MH098641A, F32 NS105324, T32 HL110852, R01 NS088566, R01 MH097104]
- NIH (NIMH Conte Center) [P50 MH094271, R35 NS097344]
Ask authors/readers for more resources
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 over-grooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available