Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation

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Title
Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation
Author(s)
Eun-Jae Lee; Hyejin Lee; Tzyy-Nan Huang; Changuk Chung; Wangyong Shin; Kyungdeok Kim; Jae-Young Koh; Yi-Ping Hsueh; Eunjoon Kim
Publication Date
2015-05
Journal
NATURE COMMUNICATIONS, v.6, no., pp.7168 -
Publisher
NATURE PUBLISHING GROUP
Abstract
Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction. Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src. Clioquinol also improves social interaction in mice haploinsufficient for the transcription factor Tbr1, which accompanies NMDAR activation in the amygdala. These results suggest that trans-synaptic Zn mobilization induced by clioquinol rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR activation. © 2015 Macmillan Publishers Limited. All rights reserved
URI
https://pr.ibs.re.kr/handle/8788114/1763
ISSN
2041-1723
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
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