Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Mice 英文参考文献.docVIP

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Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Mice 英文参考文献.doc

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Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Mice 英文参考文献

DihydrotestosteroneAmelioratesDegenerationin Muscle,AxonsandMotoneuronsandImprovesMotor FunctioninAmyotrophicLateralSclerosisModelMice Young-EunYoo,Chien-PingKo* SectionofNeurobiology,DepartmentofBiologicalSciences,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica Abstract Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT), which has both anabolic effects on muscle and neuroprotectiveeffectsonaxonsandmotoneurons,canameliorateclinicalsymptomsinALS.AsilastictubecontainingDHT crystalswasimplantedsubcutaneouslyinSOD1-G93Amiceatearlysymptomaticagewhendecreasesinbodyweightand grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscleatrophyandincreasedbodyweight,whichwasassociatedwithstrongergrip-strength.DHTtreatmentincreasedthe expressionofinsulin-likegrowthfactor-1inmuscle,whichcanexertmyotrophicaswellasneurotrophiceffectsthrough retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treatedSOD1-G93Amicedemonstratedimprovementinmotorbehaviorasassessedbyrota-rodandgaitanalyses,and anincreasedlifespan.ApplicationofDHTisarelativelysimpleandnon-invasiveprocedure,whichmaybetranslatedinto therapytoimprovethequalityoflifeforALSpatients. Citation: Yoo Y-E, Ko C-P (2012) Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in AmyotrophicLateralSclerosisModelMice.PLoSONE7(5):e37258.doi:10.1371/journal.pone.0037258 Editor:LinMei,MedicalCollegeofGeorgia,UnitedStatesofAmerica ReceivedMarch16,2012;AcceptedApril19,2012;PublishedMay14,2012 Copyright:?2012Yoo,Ko.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLic