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

Abstract:

: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_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Guo W,Murthy AC,Zhang L,Johnson EB,Schaller EG,Allan AM,Zhao X

doi

10.1093/hmg/ddr501

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

681-91

issue

3

eissn

0964-6906

issn

1460-2083

pii

ddr501

journal_volume

21

pub_type

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