Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.
Cell
; 178(4): 867-886.e24, 2019 08 08.
Article
en En
| MEDLINE
| ID: mdl-31398341
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Células Receptoras Sensoriales
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Tacto
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Agonistas del GABA
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Trastorno del Espectro Autista
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Ácidos Isonicotínicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article