Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice 英文参考文献.docVIP

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Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice 英文参考文献.doc

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Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice 英文参考文献

ReversalofGlialandNeurovascularMarkersof UnhealthyBrainAgingbyExerciseinMiddle-Aged FemaleMice CaitlinS.Latimer,JamesL.Searcy¤,MichaelT.Bridges,LawrenceD.Brewer,JelenaPopovic′, EricM. Blalock,PhilipW.Landfield,OlivierThibault,NadaM.Porter* DepartmentofMolecularandBiomedicalPharmacology,UniversityofKentuckyCollegeofMedicine,Lexington,Kentucky,UnitedStatesofAmerica Abstract Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms,manywhichhighlightitsneuroprotectiveroleviaactionsthatenhanceneurogenesis,neuronalmorphology and/orneurotrophinrelease.However,thebrainisalsocomposedofglialandvascularelements,andcomparativelylessis knownregardingtheeffectsofexerciseonthesecomponentsintheagingbrain.Here,weshowthataerobicexerciseat mid-agedecreasedmarkersofunhealthybrainagingincludingastrocytehypertrophy,ahallmarkofbrainaging.Middle- aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our resultssuggestthatage-relatedastrocytehypertrophy/reactivityandmyelindysregulationareaggravatedbyasedentary lifestyleandaccompanyingreductionsinvascularfunction.However,theseeffectsappearreversiblewithexerciseinitiated atmid-age.Asthisperiodofthelifespancoincideswiththeappearanceofmultiplemarkersofbrainaging,includinginitial signsofcognitivedecline,itmayrepresentawindowofopportunityforinterventionasthebrainappearstostillpossess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptiblethanmalestocertainriskfactorswhichcontributetovascularaging. Citation:LatimerCS,SearcyJL,BridgesMT,BrewerLD,Popovic′J,etal.(2011)ReversalofGlialandNeurovascularMarkersofUnhe