?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Elevated+glycogen+synthase+kinase+3+activity+in+Fragile+X+mice%3A+key+metabolic+regulator+with+evidence+for+treatment+potential+&rft.creator=Bauchwitz%2C+Dr.+Robert+P.&rft.subject=Neuropharmacology&rft.description=Significant+advances+have+been+made+in+understanding+the+underlying+defects+of+and+developing+potential+treatments+for+Fragile+X+Syndrome+(FXS)%2C+the+most+common+heritable+mental+retardation.+It+has+been+shown+that+neuronal+mGluR5-mediated+signaling++is+affected+in+FX+animal+models%2C+with+consequent+alterations+in+activity-dependent+protein+translation+and+synaptic+spine+functionality.+We+demonstrate+here+that+a+central+metabolic+regulatory+enzyme%2C+glycogen+synthase+kinase+3+(GSK3)+is+present+in+a+form++indicating+elevated+activity+in+several+regions+of+the+FX+mouse+brain.+Furthermore%2C+we+show+that+selective+GSK3+inhibitors%2C+as+well+as+lithium%2C+are+able+to+revert+mutant+phenotypes+of+the+FX+mouse.+Lithium%2C+in+particular%2C+remained+active+with+chronic+dosing%2C++although+its+effects+were+transient+even+when+given+from+birth.+The+combination+of+mGluR5+antagonist+and+GSK3+inhibitors+was+not+additive.+Instead%2C+it+was+discovered+that+mGluR5+signaling+and+GSK3+activation+in+the+FX+mouse+are+coordinately+elevated%2C+with++inhibition+of+mGluR5+leading+to+inhibition+of+GSK3.+These+findings+raise+the+possibility+that+GSK3+is+a+fundamental+and+central+component+of+FXS+pathology%2C+with+a+substantial+treatment+potential.++++&rft.date=2007-12-27&rft.type=Preprint&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5925%2F3%2FFX_GSK3_final_012608-HMGs_formatcorr012908.pdf&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5925%2F4%2FFX_GSK3_Supplemental_Information_012608_to_ds012908.pdf&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5925%2F5%2FMin2008-online.pdf&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5925%2F6%2FMin2008_Suppl_Info.pdf&rft.identifier=++Bauchwitz%2C+Dr.+Robert+P.++(2007)+Elevated+glycogen+synthase+kinase+3+activity+in+Fragile+X+mice%3A+key+metabolic+regulator+with+evidence+for+treatment+potential.++%5BPreprint%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F5925%2F