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Striatal Inhibition of MeCP2 or TSC1 Produces Sociability Deficits and Repetitive Behaviors

Title
Striatal Inhibition of MeCP2 or TSC1 Produces Sociability Deficits and Repetitive Behaviors
Authors
Lee, YunjinKim, HannahHan, Pyung-Lim
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2018
Journal Title
EXPERIMENTAL NEUROBIOLOGY
ISSN
1226-2560JCR Link

2093-8144JCR Link
Citation
EXPERIMENTAL NEUROBIOLOGY vol. 27, no. 6, pp. 539 - 549
Keywords
Autism spectrum disorderdorsal striatumMeCP2TSC1
Publisher
KOREAN SOC BRAIN &

NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
Indexed
SCIE; SCOPUS; KCI WOS
Document Type
Article
Abstract
Autism spectrum disorder (ASD) is a heterogeneous group of neurobehavioral disorders characterized by the two core domains of behavioral deficits, including sociability deficits and stereotyped repetitive behaviors. It is not dear whether the core symptoms of ASD are produced by dysfunction of the overall neural network of the brain or that of a limited brain region. Recent studies reported that excessive glutamatergic or dopaminergic inputs in the dorsal striatum induced sociability deficits and repetitive behaviors. These findings suggest that the dorsal striatum plays a crucial role in autistic-like behaviors. The present study addresses whether functional deficits of well-known ASD-related genes in the dorsal striatum also produce ASD core symptoms. This study also examines whether these behavioral changes can be modulated by rebalancing glutamate and/or dopamine receptor activity in the dorsal striatum. First, we found that the siRNA-mediated inhibition of Shank3,Nlgn3, Fmr1,Mecp2, or Tsc1 in the dorsal striatum produced mild to severe behavioral changes in sociability, cognition, and/or repetitive behaviors. The knockdown effects of Mecp2 and Tscl on behavioral changes were the most prominent. Next, we demonstrated that behavioral changes induced by striatal inhibition of MeCP2 and TSC1 were rescued by D-cycloserine (an NMDA agonist), fenobam (an mGluR5 antagonist), SCH23390 (a D1 antagonist), and/or ecopipam (a D1 partial antagonist), pharmacological drugs that are known to regulate ASD-like symptoms in animal models. Collectively, these results suggest that the dorsal striatum is a critical brain region that, when dystiandional, produces the core symptoms of ASD.
DOI
10.5607/en.2018.27.6.539
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일반대학원 > 뇌·인지과학과 > Journal papers
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