糖皮質(zhì)激素對神經(jīng)細胞NMDA受體亞單位基因多信號調(diào)節(jié)的影響.pdf

1、佳木斯大學碩士學位論文糖皮質(zhì)激素對神經(jīng)細胞NMDA受體亞單位基因多信號調(diào)節(jié)的影響姓名：何靜申請學位級別：碩士專業(yè)：內(nèi)分泌指導(dǎo)教師：柴國祿潘佳秋20080606Abstractobjective“Excesso￡91ucoconicoidcausesneuronaldamagewithcognitivedisordersbutthemolecularmechanismremainsunclearInthisstudyweexami—net

2、heeffectofadrenalcorticosteroidsonthetranscriptionofN—methy—Das—partate(NMDA)glutamatereceptorsubunitgenesandAlzheimerdisease(AD)relatedgenessuchasamyloidprecursorprotein(APP)，p—siteamyloidprecursorprotein—cleavingenzyme

3、l(BACE1)，andpresenilinusingneuroblasomacell1inesinvitroMethods：UsingBE(2)M17cell1ine，ahumanneuroblasomacell1ineinwkichthe：5’promoterluciferasefusiongeneisstablyincorporated，weretreatedwiththetestplasmidsNMDAglutamaterece

4、ptorsubunitgenesandAD—relatedgenesforadefindedtimeintervalanddose，andexaminedtheeffectsofglucococorficoidonthemultisignalregulationoftheratNMDA1receptorsubunitgenebya1uciferaseassayendogenousexpressionofthehumanNMDAlmRNA

5、wasexaminedbysemiquantitativeRTPCRUsingNeur02Acell1ine，aratneuroblasomacell1ineinwhichtheglutamateinducedcelltoxicityexperimentwasexamined。byCytoTox96。non—radioactivecytotoxicity，assay。kitResults：Wefoundthatsyntheticgluc

6、ocorticoiddexamethasone(dex)potentlyincreasedthepromoteractivityofNMDAland2Asubunitgenes，butdidnotstimulatethoseofAlzheimer—relatedgenesThesimilareffectofdexwasobservedonintrinsicNMDAlmRNAexpressionFuthermore。dexshowedsy

7、nergisticandadditiveeffectswithproteinkinaseAandC—mediatedsignalingpathways，respectivelyFinallytreatmentoftheNeur02Acells，whichexpressintrinsicglucocorticoidreceptor’withdexsignificantlyenhancedtheglutamate—inducedneurot

8、oxicityConclusion：Ourresultssuggestthatglucocorticoidinducedneuronaldamagemaybe，at1eastpartlyattributabletoenhancedexpressionofglutamateNMDAreceptorwithresultantincreaseinthesusceptibilityofglutamateinducedexcitotoxicity