Reducing vascular cognitive impairment within and across generations by epigenetic conditioning
通过表观遗传调节减少代内和代际间的血管性认知障碍
基本信息
- 批准号:10212499
- 负责人:
- 金额:$ 40.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAcuteAdultAlzheimer&aposs DiseaseAnimalsBilateralBiologicalBlood PressureBrainBrain InjuriesCarotid StenosisCerebral IschemiaCholinesterase InhibitorsChronicClinical TrialsDNADataDeacetylationDementiaDevicesDiseaseEnzymesEpidemiologyEpigenetic ProcessExhibitsFathersFutureGene ExpressionGene Expression RegulationGene-ModifiedGenerationsGenesGenetic TranscriptionGerm CellsGlaucomaHDAC3 geneHeritabilityHippocampus (Brain)Histone Deacetylase InhibitorHistonesHumanHypoxiaImpaired cognitionIntentionIntergenerational transferInvestigationLong-Term PotentiationMeasuresMediatingMemory LossMessenger RNAModelingModificationMolecularMothersMusMyocardial IschemiaNeurocognitiveNeurocognitive DeficitObservational StudyOrganismOutcome StudyParentsPartner in relationshipPatternPharmacological TreatmentPhenotypePlantsPlayPrefrontal CortexProblem SolvingProcessProteinsPublic HealthRadialRepressionResearchRetinal Ganglion CellsRoleSecondary toSeedsShort-Term MemorySideSkeletal MuscleSomatic CellStimulusStressStrokeSynaptic plasticityTestingTherapeuticThinkingTissuesTranscriptional RegulationVascular Cognitive Impairmentacute strokeaging populationarmbasecell injurycerebral hypoperfusionchronic neurologic diseasecognitive functioncohortconditioningdesigndiet and exercisedisorder riskdonepezilefficacious treatmentepigenetic regulationexecutive functionexperiencehigh rewardhigh riskin vivoinsightintergenerationalmemory recognitionmouse modelneurovascularnon-genomicnovelobject recognitionpreclinical studypreconditioningpreservationpreventprogramsprogressive neurodegenerationresilienceresponsespatial memorystressorvascular cognitive impairment and dementiavascular risk factor
项目摘要
PROJECT SUMMARY
Neurocognitive impairment secondary to vascular contributions to cognitive impairment and dementia (VCID)
exacts devastating tolls on our aging population, and to date, efficacious therapies remain elusive. Epigenetics-
based therapeutics hold promise in this regard, as growing evidence continues to document the epigenetic
induction of beneficial, disease-resilient phenotypes in response to distinct patterns of “positive stress”
(`eustress'). Such profound findings indicate that reprogramming the activation and repression of a broad array
of innate genes can actually protect the brain from injury in the absence of any exogenous, pharmacologic
treatment. Indeed, recent findings from our lab using a well-established model of VCID indicate that repetitively
conditioning mice with brief periods of nonharmful systemic hypoxia (RHC) prevents memory loss in vivo, and
preserves hippocampal synaptic plasticity ex vivo, caused by three months of chronic cerebral hypoperfusion
secondary to bilateral carotid artery stenosis. Moreover, we have discovered that adult, first-generation progeny
of mice that were treated with RHC prior to mating also exhibit these same VCID-resilient phenotypes – in the
absence of any direct treatment. Thus, the present proposal is founded on the overall hypothesis that adaptive
epigenetics-based treatments can prevent VCID-associated cognitive loss, both within and across generations.
Studies in Aim 1 are designed to determine if the aforementioned intergenerational protection against cognitive
impairment that results from parental RHC requires treatment of both parents, or only the father or mother. The
outcome of these studies will inform future studies of germ cell epigenetic change that ultimately underlies this
transfer of induced, beneficial phenotypes. Studies in Aim 2 are designed to start unraveling the epigenetic
regulatory mechanisms responsible for the protection against VCID-associated cognitive impairment in mice
directly treated with RHC, focusing specifically on histone deacetylase 3 (HDAC3) and the role it plays in the
transcriptional regulation of genes that contribute to RHC-mediated dementia resilience. Results of these studies
will begin to build a molecular framework for how histone-based epigenetic modifications of gene expression can
prevent memory loss in VCID. Overall, our investigations will provide mechanistic insights into the efficacious
and ongoing clinical trials of remote conditioning for VCID, a translational counterpart of our RHC therapy that
involves inducing repetitive cycles of skeletal muscle hypoxia with blood pressure cuff devices. And they will
plant the seeds for advancing epidemiological and epigenetic research programs to explore the exciting
possibility that an induced resilience to VCID may be heritable in humans as well.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Maternal repetitive hypoxia prior to mating confers epigenetic resilience to memory impairment in male progeny.
交配前母体反复缺氧赋予雄性后代记忆障碍的表观遗传恢复能力。
- DOI:10.1037/bne0000554
- 发表时间:2023
- 期刊:
- 影响因子:1.9
- 作者:Broyles,EmreyE;Corell,DavidH;Gidday,JeffreyM
- 通讯作者:Gidday,JeffreyM
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JEFFREY M GIDDAY其他文献
JEFFREY M GIDDAY的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JEFFREY M GIDDAY', 18)}}的其他基金
Vascular Mechanisms of Cerebral Ischemic Tolerance
脑缺血耐受的血管机制
- 批准号:
7446769 - 财政年份:2005
- 资助金额:
$ 40.43万 - 项目类别:
Vascular Mechanisms of Cerebral Ischemic Tolerance
脑缺血耐受的血管机制
- 批准号:
7248172 - 财政年份:2005
- 资助金额:
$ 40.43万 - 项目类别:
Vascular Mechanisms of Cerebral Ischemic Tolerance
脑缺血耐受的血管机制
- 批准号:
6967502 - 财政年份:2005
- 资助金额:
$ 40.43万 - 项目类别:
相似海外基金
Un/kindness, shame & resistance: the care of inpatients in NHS adult acute mental health units and how it might be improved
Un/善良,羞耻
- 批准号:
2885806 - 财政年份:2023
- 资助金额:
$ 40.43万 - 项目类别:
Studentship
Post-Acute Care Transitions for Older Adult Medicare Beneficiaries with Serious Mental Illness
患有严重精神疾病的老年医疗保险受益人的急性后护理过渡
- 批准号:
10772386 - 财政年份:2023
- 资助金额:
$ 40.43万 - 项目类别:
Paving The Way to a Canadian Standard of Care with CAR-T Cellular Therapy: Phase II Trial of CD19 CAR-T for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia (CLIC-01A)
通过 CAR-T 细胞疗法为加拿大护理标准铺平道路:CD19 CAR-T 治疗复发/难治性成人急性淋巴细胞白血病的 II 期试验 (CLIC-01A)
- 批准号:
474619 - 财政年份:2022
- 资助金额:
$ 40.43万 - 项目类别:
Operating Grants
Investigating the impact acute inhalation of cannabis with a high content of delta-9-tetrahydrocannabinol has on myelination and microglia in adult and aged mice
研究急性吸入高含量 delta-9-四氢大麻酚的大麻对成年和老年小鼠髓鞘形成和小胶质细胞的影响
- 批准号:
485965 - 财政年份:2022
- 资助金额:
$ 40.43万 - 项目类别:
Studentship Programs
Paving The Way to a Canadian Standard of Care with CAR-T Cellular Therapy: Phase II Trial of CD19 CAR-T for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia (CLIC-01A)
通过 CAR-T 细胞疗法为加拿大护理标准铺平道路:CD19 CAR-T 治疗复发/难治性成人急性淋巴细胞白血病的 II 期试验 (CLIC-01A)
- 批准号:
466358 - 财政年份:2022
- 资助金额:
$ 40.43万 - 项目类别:
Operating Grants
Metabolomics for prediction of cisplatin mediated acute kidney injury: a Canadian multi-centre adult and pediatric study
预测顺铂介导的急性肾损伤的代谢组学:加拿大多中心成人和儿童研究
- 批准号:
402040 - 财政年份:2019
- 资助金额:
$ 40.43万 - 项目类别:
Operating Grants
Study of pathogenic mechanism of age-dependent chromosome translocation in adult acute lymphoblastic leukemia
成人急性淋巴细胞白血病年龄依赖性染色体易位发病机制研究
- 批准号:
18K16103 - 财政年份:2018
- 资助金额:
$ 40.43万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Causal effect of time-varying driving pressures on mortality in mechanically ventilated, adult patients with acute respiratory distress syndrome
时变驱动压力对机械通气成年急性呼吸窘迫综合征患者死亡率的因果影响
- 批准号:
377313 - 财政年份:2017
- 资助金额:
$ 40.43万 - 项目类别:
Studentship Programs
Role of SETBP1 in adult Ph+ acute lymphoblastic leukemia
SETBP1 在成人 Ph 急性淋巴细胞白血病中的作用
- 批准号:
9315111 - 财政年份:2016
- 资助金额:
$ 40.43万 - 项目类别:
Acute Inhibition of Adult-born Granule Cells and its Effect on Antidepressant Act
成体颗粒细胞的急性抑制及其抗抑郁作用
- 批准号:
8734273 - 财政年份:2013
- 资助金额:
$ 40.43万 - 项目类别:














{{item.name}}会员




