Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

Traduction partielle : G.M.

Neuropsychopharmacology. 2013 Oct 7. doi: 10.1038/npp.2013.274. [Epub ahead of print]

L'augmentation de l'acétylcholine allège la  rigidité cognitive et le déficit social dans un modèle murin de l'autisme

Karvat G, Kimchi T.

Source

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Abstract

Autism spectrum disorders (ASD) is defined by behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests/ cognitive rigidity. Recent studies in humans and mice suggested that dysfunction of the cholinergic system may underlie autism-related behavioral symptoms. Here we tested the hypothesis that augmentation of acetylcholine in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI) Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was injected directly into the rodent homologue of the caudate nucleus, the dorso-medial-striatum (DMS), of the inbred mouse strain BTBR T+tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes and expressing low brain acetylcholine levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference and enhancing social interaction, in a dose dependent manner. Microinjection of the drug directly into the DMS, but not into the ventromedial striatum, led to significant amelioration of the cognitive-rigidity and social-deficiency phenotypes. 
Pris ensemble, ces résultats fournissent la preuve du rôle clé du système cholinergique et du stratium dorso-medial dans l'étiologie des TSA, et suggèrent que la flexibilité cognitive élevée peut provoquer une attention sociale accrue.
L'effet thérapeutique potentiel de AChEIs chez les patients atteints de TSA est discutée.

PMID: 24096295