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Monday, June 8, 2015

Increases in Zn Concentration in Mouse Brains Reduce Autism-like Behaviors


Taiwan: Two research teams have discovered that increases in zinc reduce social defects in two mouse models of autism. The research was published in Nature Communications on May 18, 2015. Drs. Kim’s and Hsueh’s laboratories demonstrated that administration of the clinical drug clioquinol increases zinc in a certain part of mouse brains resulting in the noticeable improvement of social defects in the two types of mice. Using established autism mouse models (Shank2-/- and Tbr1+/- mice), members of the two laboratories demonstrated that mobilization of zinc from presynaptic termini to the postsynaptic sites of neurons induced by clioquinol enhances postsynaptic protein kinase activity and thus rescues the activation of NMDAR, one of the major excitatory ion channels in the central nervous system. This finding explains the role of zinc in neuronal activation and provides a potential therapy for autism spectrum disorders (ASDs).
ASDs are one of most common neurodevelopmental disorders. Both genetic and environmental factors are involved in the etiology of ASDs. Zinc deficiency is frequently associated with ASDs, but the mechanism underlying the role of zinc deficiency in ASDs is unclear. According to research published in the journal Scientific Reports in 2011, an examination of the hair of 1,967 children with autistic disorders (1,553 males and 414 females) showed that almost 30% had low zinc concentrations.

In this work, Dr. Kim’s lab carried out the Shank2 study and Dr. Hsueh’s lab analyzed the effect of Cq on Tbr1 mutant mice, which was conducted by Dr. Tzyy-Nan Huang. The study of Tbr1 mutant mice was supported by the Frontier Research Grant of the Ministry of Science and Technology to Dr. Hsueh. Dr. Huang is supported by the Postdoctoral Fellowship of Academia Sinica.

The full article entitled “Trans-synaptic Zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation” is available at Nature Communications website at: http://www.nature.com/ncomms/2015/150518/ncomms8168/full/ncomms8168.html