Effects of Aging on Blood Vessels in the Cerebellar Vermis
衰老对小脑蚓部血管的影响
基本信息
- 批准号:9895600
- 负责人:
- 金额:$ 18.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2022-01-31
- 项目状态:已结题
- 来源:
- 关键词:Accident and Emergency departmentAffectAgeAgingAnteriorAttenuatedBiological ProcessBlood VesselsBlood VolumeBlood flowBrainBrain regionCell DeathCellsCerebellar DiseasesCerebellar vermis structureCerebellumCerebrovascular CirculationCerebrumDegenerative DisorderDiffusion Magnetic Resonance ImagingDiseaseElderlyEndotheliumEquilibriumFunctional disorderGaitGlutathioneGoalsHealthHippocampus (Brain)HumanImpairmentIndividualInferiorKnowledgeLateralLeadLobeLobuleLocomotionMicrocirculationMolecularMotorMotor CortexMusNatureNerve DegenerationNeuronal DysfunctionNeuronsOlives - dietaryOutcomeOxidation-ReductionOxidative StressPersonsPontine structurePosturePrefrontal CortexPurkinje CellsResearchRiskRoleSIRT1 geneSeveritiesStatistical Data InterpretationStructureTestingTissuesVascular DiseasesVascular SystemWorkage differenceage effectage relatedagedaging brainarea striataentorhinal cortexexperimental studyfallshuman old age (65+)imaging studyimprovedinjury-related deathmotor controlmotor deficitmotor disorderneuron lossoxidative damagesenescencewhite matter
项目摘要
Abstract
Aging is a fundamental biological process accompanied by a general decline in tissue function and
increased risk for many diseases. Indeed, decline in fine motor control, gait and balance is among the
most important health problems in the elderly. Although the mechanism underlying cerebellar
dysfunction is unclear, compelling evidence indicate that when the cerebellum ages, it starts to shrink
in volume as a whole in the mid-fifties of humans. Looking particularly at the lobules as a whole, the
anterior lobules (vermis) that control bodily posture and locomotion are most significantly affected by
aging, but not the lateral portions of the cerebellum. It is well-known that aging-related structural and
functional disturbances in the macro- or microcirculation of the brain lead to brain degeneration and
dysfunction. However, whether aging impairs vascular structure and function of cerebellum is largely
unknown. Our preliminary study showed that the number and volume of blood vessels were selectively
reduced in vermis of cerebellum in aged mice, along with increased glutathione redox state, but the
hippocampus was not affected. Thus, our central hypothesis is that: aging selectively impairs the
vascular structure and function in vermis of cerebellum, which, in turn, increase oxidative damage in
these regions, leading to neuronal dysfunction or loss and motor deficits. Our SPECIFIC AIM is to (1)
determine whether aging selectively impairs vascular structure and function in the vermis of cerebellum,
compared to other cerebellar and cerebral regions. (2) Determine whether aging increases oxidative
stress and neurodegeneration in the vermis of cerebellum, compared to other cerebellar and cerebral
regions. (3) Explore whether improved cerebral blood flow via increase of endothelial NAD+-SIRT1
activity reduces oxidative stress and attenuates neurodegeneration in the vermis of cerebellum and
improve age-related cerebellar motor dysfunction. The rationale for the proposed research is that
successful completion of the proposed experiments will provide missing, fundamental knowledge
regarding the impact of the aging on vessel structure and function, and potential mechanisms underlying
motor dysfunction in elderly.
抽象的
衰老是一个基本的生物过程,伴随着组织功能的总体下降和
增加了许多疾病的风险。实际上,良好的运动控制,步态和平衡的下降是
老年人最重要的健康问题。虽然小脑的基础机制
功能障碍尚不清楚,令人信服的证据表明,当小脑年龄时,它开始缩小
在整个人类中,整个体积。特别看着整个小叶,
控制身体姿势和运动的前叶(vermis)最显着影响
衰老,但不是小脑的横向部分。众所周知,与衰老相关的结构和
大脑宏观或微循环中的功能障碍导致脑退化,并且
功能障碍。但是,衰老是否会损害小脑的血管结构和功能很大
未知。我们的初步研究表明,血管的数量和数量是选择性的
老年小鼠小脑的vermis降低,以及谷胱甘肽氧化还原状态增加,但
海马不受影响。因此,我们的中心假设是:衰老有选择地损害
小脑vermis中的血管结构和功能,进而增加氧化损伤
这些区域导致神经元功能障碍或损失和运动缺陷。我们的具体目的是(1)
确定衰老是否有选择地损害小脑vermis中的血管结构和功能,
与其他小脑和大脑区域相比。 (2)确定衰老是否增加氧化
与其他小脑和大脑相比
地区。 (3)探索是否通过增加内皮NAD+-SIRT1来改善大脑血流
活性减少氧化应激,并减轻小脑vermis中的神经退行性
改善与年龄有关的小脑运动功能障碍。拟议研究的理由是
成功完成拟议的实验将提供缺失的基本知识
关于老化对血管结构和功能的影响以及潜在机制
老年人的运动功能障碍。
项目成果
期刊论文数量(0)
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Kunlin Jin其他文献
Kunlin Jin的其他文献
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