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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Disease Models, Animal
-
Fragile X Mental Retardation Protein / genetics
-
Fragile X Syndrome / enzymology*
-
Fragile X Syndrome / pathology
-
Fragile X Syndrome / physiopathology
-
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
-
Glycogen Synthase Kinase 3 / metabolism
-
Glycogen Synthase Kinase 3 beta
-
Hippocampus / drug effects*
-
Hippocampus / physiopathology
-
Indoles / pharmacology*
-
Learning / drug effects*
-
Male
-
Maleimides / pharmacology*
-
Mice
-
Mice, Knockout
-
Nerve Net
-
Neurogenesis / drug effects*
-
Neurons / drug effects
-
Neurons / ultrastructure
-
Phosphorylation / drug effects
-
Protein Kinase Inhibitors / pharmacology*
Substances
-
Fmr1 protein, mouse
-
Indoles
-
Maleimides
-
Protein Kinase Inhibitors
-
SB 216763
-
Fragile X Mental Retardation Protein
-
Glycogen Synthase Kinase 3 beta
-
Gsk3b protein, mouse
-
Glycogen Synthase Kinase 3