Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models
Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models
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DOI：
10.1016/j.cell.2019.07.024
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发表时间：
2019-08-08
期刊：
影响因子：
64.5
通讯作者：
Ginty, David D.
中科院分区：
文献类型：
--
作者：
Orefice, Lauren L.;Mosko, Jacqueline R.;Ginty, David D.
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.
