Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice

Item Type:	Article
Title:	Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice
Creators Name:	Lim, C.S. and Kim, H. and Yu, N.K. and Kang, S.J. and Kim, T.H. and Ko, H.G. and Lee, J. and Yang, J.E. and Ryu, H.H. and Park, T. and Gim, J. and Nam, H.J. and Baek, S.H. and Wegener, S. and Schmitz, D. and Boeckers, T.M. and Lee, M.G. and Kim, E. and Lee, J.H. and Lee, Y.S. and Kaang, B.K.
Abstract:	Autism spectrum disorders (ASDs) are a group of developmental disorders that cause variable and heterogeneous phenotypes across three behavioral domains such as atypical social behavior, disrupted communications, and highly restricted and repetitive behaviors. In addition to these core symptoms, other neurological abnormalities are associated with ASD, including intellectual disability (ID). However, the molecular etiology underlying these behavioral heterogeneities in ASD is unclear. Mutations in SHANK2 genes are associated with ASD and ID. Interestingly, two lines of Shank2 knockout mice (e6-7 KO and e7 KO) showed shared and distinct phenotypes. Here, we found that the expression levels of Gabra2, as well as of GABAA receptor-mediated inhibitory neurotransmission, are reduced in Shank2 e6-7, but not in e7 KO mice compared with their own wild type littermates. Furthermore, treatment of Shank2 e6-7 KO mice with an allosteric modulator for the GABAA receptor reverses spatial memory deficits, indicating that reduced inhibitory neurotransmission may cause memory deficits in Shank2 e6-7 KO mice.
Keywords:	Autism Spectrum Disorders, Shank2, Gabra2, I/E Ratio, Spatial Memory, Animals, Mice
Source:	Neuropharmacology
ISSN:	0028-3908
Publisher:	Elsevier
Volume:	112
Number:	Part A
Page Range:	104-112
Date:	January 2017
Official Publication:	https://doi.org/10.1016/j.neuropharm.2016.08.016
PubMed:	View item in PubMed

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