Aβ损伤对大鼠脑内神经甾体合成代谢的影响及孕酮保护作用及机制研究的开题报告.docx

Aβ损伤对大鼠脑内神经甾体合成代谢的影响及孕酮保护作用及机制研究的开题报告

ResearchTitle:TheEffectsofAβInjuryonNeurosteroidSynthesisandMetabolisminRatBrainandtheProtectiveRoleofProgesterone,anditsMechanismofAction.

Introduction

Theaccumulationofamyloid-β(Aβ)peptidehasbeenconsideredacriticalcontributortothepathogenesisofAlzheimersdisease(AD),aneurodegenerativedisordercharacterizedbyprogressivecognitivedeclineandneuroinflammation.Aβinjuryleadstoneuroinflammationandimpairsthemechanismsofbrainneurosteroidsynthesisandmetabolism,whichhaveanimpactonvariousneurologicalfunctionsandbehavior.Therefore,studyingtheimpactofAβinjuryonneurosteroidmetabolismandunderstandingtheprotectiveroleofprogesteroneagainstAβ-inducedneuroinflammationarecriticalstepstowarddevelopingeffectivetherapeuticapproachesforAD.

Objectives

TheprimaryobjectiveofthisresearchistoinvestigatethechangesinneurosteroidsynthesisandmetabolismintheratbrainfollowingAβinjuryandtodeterminethemechanismthatunderliesthesechanges.ThestudyalsoaimstoexaminetheneuroprotectiveeffectsofprogesteroneonAβ-inducedneuroinflammationanditsrelationshipwithneurosteroidmetabolism.

Methodology

ThisstudywillinvolvetheuseofmaleWistarrats,whichwillbedividedintofourgroups(A,B,C,andD).GroupAwillserveasthecontrolgroupandwillreceiveasalineinjection.GroupBwillreceiveasingleinjectionofAβ,whichwillinduceneuroinflammation.GroupCwillreceivechronicprogesteronetreatment(20mg/kg/day)fortwoweeksbeforetheAβinjectiontodeterminetheprotectiveeffectsofprogesteroneonthebrainagainstAβinjury.GroupDwillreceiveacombinationofAβandprogesteronetreatment.

Thelevelsofneurosteroids,suchaspregnenolone,progesterone,andallopregnanolone,willbemeasuredinthebraintissueusingliquidchromatographyandtandemmassspectrometry.Theexpressionlevelsofgenes