title: 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.
authors: Waisman Center and Department of Neuroscience, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
authors: Weixiang
authors: W
authors: Guo
authors: Adeline C
authors: AC
authors: Murthy
authors: Li
authors: L
authors: Zhang
authors: Eric B
authors: EB
authors: Johnson
authors: Eric G
authors: EG
authors: Schaller
authors: Andrea M
authors: AM
authors: Allan
authors: Xinyu
authors: X
authors: Zhao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; C497684:Fmr1 protein, mouse; C417521:SB 216763; C000605507:Gsk3b protein, mouse