Journal Article

Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome

Weixiang Guo, Adeline C. Murthy, Li Zhang, Eric B. Johnson, Eric G. Schaller, Andrea M. Allan and Xinyu Zhao

in Human Molecular Genetics

Volume 21, issue 3, pages 681-691
Published in print February 2012 | ISSN: 0964-6906
Published online November 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr501
Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome

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Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates the adult neural stem cell fate through the translational regulation of glycogen synthase kinase 3β (GSK3β), we investigated the effects of a GSK3β inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3β could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3β inhibition as a potential treatment for the learning deficits seen in FXS.

Journal Article.  7430 words.  Illustrated.

Subjects: Genetics and Genomics

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