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1、DonepezilrescuesthemedicalseptumcholinergicneuronsvianicotinicAChrecepDonepezilrescuesthemedicalseptumcholinergicneuronsvianicotinicAChreceptorstimulationinolfactorybulbectomizedmiceYuiYamamoto,KohjiFukunaga*DepartmentofPharmacology,GraduateSchoolofPharmaceuticalS
2、cience,TohokuUniversity,Sendai,Japan;*CorrespondingAuthor:kfukunagam.tohoku.ac.jpReceived12September2013;revised20October2013;accepted1November2013Copyright©2013YuiYamamoto,KohjiFukunaga.ThisisanopenaccessarticledistributedundertheCreativemonsAttributionLicen
3、se,itsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginaly(OBX)causescognitivedysfunctionbydegenerationofcholinergicneuronsinthemedialseptum.Here,entofnicotinicacetylcholinereceptor(nAChR)inneuroprotectiveeffectofdonepezilintheseptumneurons
4、ofOBXmice.NeuroprotectiveeffectsonthemedialseptalcholinergicneuronsinistrationinOBXmice.),anicotinicacetylcholinereceptorantagonist.DonepezilincreasesphosphorylationofAktandERKvianAChRstimulationinthemedialseptumcholinergicneurons.TheAktandERKstimulationbydonepezi
5、lisassociatededialseptumandmemoryimprovement.Key;NicotinicAcetylcholineReceptors1.INTRODUCTIONDestructionofolfactorysystemreportedlyimpairslearningandmemory[1-3]andAlzheimer’sdisease(AD)patientsshopairmentofolfactorybulbfunctionsevenintheearlystage[4,5].Thecholine
6、rgicneuronsinthebasalforebrainandolfactorybulbareoriginatedfromthemedialseptum,therebyprovidingcholinergicinnervationtothehippocampus,olfactoryblub,amygdalaandoverallneocortex[6].Interestingly,olfactorybulbectomy(OBX)causesdegenerationofcholinergicneuronsnotonlyin
7、themedialseptumbutalsointhehippocampus,therebyelicitinghippocampus-dependentmemorydeficitsinmice[7].Insupporttothisidea,OBXtreatmentelicitsreductionofacetylcholinesterase(AChE)andcholineacetyltransferase(ChAT)levelsinthehippocampus[8,9]andnicotine-inducedacetylcho
8、line(ACh)releaseinthehippocampuspairedinOBXmice[10].Inaddition,significantelevationofbetaamyloid(Aβ)levelsisseeninextractsfromneocortexandhippocampusbyO
