Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

Autor: Orefice LL; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Mosko JR; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Morency DT; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Wells MF; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, MA 02139, USA., Tasnim A; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Mozeika SM; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Ye M; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Chirila AM; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Emanuel AJ; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Rankin G; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Fame RM; Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA., Lehtinen MK; Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA., Feng G; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, MA 02139, USA., Ginty DD; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: david_ginty@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Cell [Cell] 2019 Aug 08; Vol. 178 (4), pp. 867-886.e24.
DOI: 10.1016/j.cell.2019.07.024
Abstrakt: 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 overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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