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标题：Rapamycin suppresses brain aging in senescence-accelerated OXYS rats
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作者：Nataliya G. Kolosova ; Anton O.Vitovtov ; Natalia A Muraleva 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：6
页码：474-484
出版社：U.S.Department of Health & Human Service
摘要：Cellular.and. organismal. aging. are. driven. in. part. by. the. MTOR. (mechanistic. target. of. rapamycin).pathway. andrapamycin.extends.life.span.in.C.elegans,.Drosophila.and.mice..Herein,.we.investigated.effects.of.rapamycin.on.brain.agingin.OXYS. rats.. Previously. we. found,. in. OXYS. rats,.an. early.development.of.age©\associated. pathological. phenotypes. similarto. several. geriatric. disorders. in. humans,. including. cerebral. dysfunctions.. Behavioral. alterations. as. well. as. learning. andmemory.deficits.develop.by.3.months.. Here.we.show. that. rapamycin.treatment.(0.1.or.0.5. mg/kg. as. a.food.mixture.dailyfrom.the.age. of. 1.5. to. 3.5. months). decreased.anxiety. and.improved. locomotor.and. exploratory.behavior.in.OXYS. rats.. Inuntreated. OXYS. rats,. MRI. revealed. an. increase. of. the. area. of. hippocampus,. substantial. hydrocephalus. and. 2©\foldincreased. area. of. the. lateral. ventricles.. Rapamycin. treatment. prevented. these. abnormalities,. erasing. the. differencebetween.OXYS.and.Wistar.rats.(used.as. control)..All.untreated.OXYS.rats.showed.signs.of.neurodegeneration,.manifestedby. loci. of. demyelination.. Rapamycin. decreased. the. percentage. of. animals. with. demyelination. and. the. number. of. loci.Levels. of. Tau. and. phospho©\Tau. (T181). were. increased. in. OXYS. rats. (compared. with. Wistar).. Rapamycin. significantlydecreased. Tau. and. inhibited. its. phosphorylation. in. the. hippocampus. of. OXYS. and. Wistar. rats.. Importantly,. rapamycintreatment.caused. a. compensatory. increase. in. levels. of.S6. and.correspondingly. levels. of. phospo©\S6.in. the. frontal. cortex,indicating. that.some. downstream. events. were. compensatory.preserved,. explaining.the.lack. of.toxicity.. We.conclude. thatrapamycin.in.low.chronic.doses.can.suppress.brain.aging
关键词：aging;.MTOR;.mTOR;.brain;.age©\related.diseases