Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntingtons Disease Transgenic Mice 英文参考文献.docVIP

Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntingtons Disease Transgenic Mice 英文参考文献.doc

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Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntingtons Disease Transgenic Mice 英文参考文献

SomatostatinReceptor1and5DoubleKnockoutMice MimicNeurochemicalChangesofHuntington’sDisease TransgenicMice PadmeshS.Rajput1,GeetanjaliKharmate1,MichaelNorman2,Shi-HeLiu2,BhagavatulaR.Sastry3, CharlesF.Brunicardi2,UjendraKumar1* 1DivisionofPharmacologyandToxicology,FacultyofPharmaceuticalSciences,TheUniversityofBritishColumbia,Vancouver,BritishColumbia,Canada,2Departmentof Surgery,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica,3NeuroscienceResearchLaboratory,DepartmentofAnesthesiology,Pharmacologyand Therapeutics,TheUniversityofBritishColumbia,Vancouver,BritishColumbia,Canada Abstract Background:Selectivedegenerationofmediumspinyneuronsandpreservationofmediumsizedaspinyinterneuronsin striatumhasbeenimplicatedinexcitotoxicityandpathophysiologyofHuntington’sdisease(HD).However,themolecular mechanismfortheselectivesparingofmediumsizedaspinyneuronsandvulnerabilityofprojectionneuronsisstillelusive. ThepathologicalcharacteristicofHDisanextensivereductionofthestriatalmass,affectingcaudateputamen.Somatostatin (SST) positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimicthemodelofHD.SSTplaysneuroprotectiveroleinexcitotoxicityandthebiologicaleffectsofSSTaremediatedby fivesomatostatinreceptorsubtypes(SSTR1-5). MethodsandFindings:TodelineatesubtypeselectivebiologicalresponseswehavehereinvestigatedchangesinSSTR1 and5doubleknockoutmicebrainandcomparedwithHDtransgenicmousemodel(R6/2).Ourstudyrevealedsignificant lossofdopamineandcAMPregulatedphosphoproteinof32kDa(DARPP-32)andcomparablechangesinSST,N-methyl-D- asparticacidreceptorssubtypes,calbindinandbrainnitricoxidesynthaseexpressionaswellasinkeysignalingproteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-a and calcineurin in SSTR1/52/2 and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidy- linositol 3-kinases were strain specific. SSTR1/5 appears

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