Regulation of Neurogenesis and Cognition by Systemic Age-Related Immune Factors
全身年龄相关免疫因子对神经发生和认知的调节
基本信息
- 批准号:8546253
- 负责人:
- 金额:$ 36.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-15 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenovirusesAdultAffectAgingAging-Related ProcessAlzheimer&aposs DiseaseAnimalsBloodBrainCCL11 geneCCL2 geneCell Culture TechniquesCell ProliferationCell physiologyCellsCoculture TechniquesCognitionCognitiveComplementDegenerative DisorderEnvironmentExposure toFunctional disorderGoalsHippocampus (Brain)ImmuneImpaired cognitionImpairmentIn VitroInjection of therapeutic agentLaboratoriesLearningMediatingMemoryMethodsMicrogliaMolecularMusNatural regenerationNervous system structureNeuraxisNeurodegenerative DisordersOrganParabiosisPathway interactionsProcessProteinsRNA InterferenceRadialRecombinantsRegulationResearchRoleSignal TransductionStem cellsTestingTherapeuticTissuesTrainingViralVirusWaterWorkadult neurogenesisage effectage relatedaging brainarmbasecell typecognitive functionconditioned fearenvironmental changein vivointerestnerve stem cellneurogenesisnormal agingpublic health relevancereceptorreceptor expressionregenerativerelating to nervous systemrepairedresponseretroviral-mediatedself-renewalstemtissue repair
项目摘要
DESCRIPTION (provided by applicant): Stem cells have been the focus of numerous scientific endeavors due to their potential for mediating enhanced tissue repair, regeneration from degenerative diseases, and amelioration of age-related organ dysfunction. The possibility of harnessing stem cells to reverse normal aging raises the question as to how the aging process modulates tissue specific stem cell activity. In the central nervous system, investigating the effect of aging on neural stem/progenitor cell (NPC) function is of particular interest due to the associated onset of cognitive impairments, and lack of neural repair in response to neurodegenerative diseases, such as Alzheimer's disease. During my doctoral work, I discovered that molecular changes occurring in the aging systemic milieu negatively regulate NPC function and cognition. Furthermore, I identified a subset of systemic immune factors - ¿2-Microglobulin (B2M), CCL11 and CCL2 -, as potential regulators of neurogenesis and cognitive function. Interestingly, immune signaling has emerged as a key player in the negative regulation of adult neurogenesis. Thus, the goal of this application is to investigate how immune-related molecular changes in the aging systemic milieu regulate NPC function and associated cognitive processes. Specifically, my hypothesis is that systemic age-related immune factors impair neurogenesis, and cognitive processes, by both inhibiting NPC function directly and indirectly via resident immune cells. I will address this hypothesis in three aims: 1.To determine the direct versus indirect effect of systemic age-related immune factors on NPC function in vitro, 2. To examine the direct effect of systemic age-related immune factors on neurogenesis and cognitive function in vivo, 3. To explore the indirect effect of systemic age-related immune factors mediated by resident immune cells on neurogenesis and cognitive function in vivo. Ultimately, I hope that by investigating the cellular and molecular mechanisms underlying impairments in NPC function, we can better understand how to ameliorate age-related cognitive dysfunction by harnessing the latent plasticity remaining within the old brain.
DESCRIPTION (provided by applicant): Stem cells have been the focus of numerous scientific endeavors due to their potential for mediating enhanced tissue repair, regeneration from degenerative diseases, and amelioration of age-related organ dysfunction. The possibility of harnessing stem cells to reverse normal aging raises the question as to how the aging process modulates tissue specific stem cell activity. In the central nervous system, investigating the effect of aging on neural stem/progenitor cell (NPC) function is of particular interest due to the associated onset of cognitive impairments, and lack of neural repair in response to neurodegenerative diseases, such as Alzheimer's disease. During my doctoral work, I discovered that molecular changes occurring in the aging systemic milieu negatively regulate NPC function and cognition. Furthermore, I identified a subset of systemic immune factors - ¿2-Microglobulin (B2M), CCL11 and CCL2 -, as potential regulators of neurogenesis and cognitive function. Interestingly, immune signaling has emerged as a key player in the negative regulation of adult neurogenesis. Thus, the goal of this application is to investigate how immune-related molecular changes in the aging systemic milieu regulate NPC function and associated cognitive processes. Specifically, my hypothesis is that systemic age-related immune factors impair neurogenesis, and cognitive processes, by both inhibiting NPC function directly and indirectly via resident immune cells. I will address this hypothesis in three aims: 1.To determine the direct versus indirect effect of systemic age-related immune factors on NPC function in vitro, 2. To examine the direct effect of systemic age-related immune factors on neurogenesis and cognitive function in vivo, 3. To explore the indirect effect of systemic age-related immune factors mediated by resident immune cells on neurogenesis and cognitive function in vivo. Ultimately, I hope that by investigating the cellular and molecular mechanisms underlying impairments in NPC function, we can better understand how to ameliorate age-related cognitive dysfunction by harnessing the latent plasticity remaining within the old brain.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
SAUL A VILLEDA其他文献
SAUL A VILLEDA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('SAUL A VILLEDA', 18)}}的其他基金
Pro-youthful role of Gpld1 on regenerative and cognitive function in the aged brain
Gpld1 对老年大脑再生和认知功能的促年轻作用
- 批准号:
10621267 - 财政年份:2022
- 资助金额:
$ 36.75万 - 项目类别:
Role of exercise-induced blood factors in rejuvenating the aged brain
运动诱发的血液因子在恢复衰老大脑活力中的作用
- 批准号:
10615716 - 财政年份:2020
- 资助金额:
$ 36.75万 - 项目类别:
Role of exercise-induced blood factors in rejuvenating the aged brain
运动诱发的血液因子在恢复衰老大脑活力中的作用
- 批准号:
10380830 - 财政年份:2020
- 资助金额:
$ 36.75万 - 项目类别:
Investigating the pro-aging role of B2M and MHC molecules on regenerative and cognitive function in the brain
研究 B2M 和 MHC 分子对大脑再生和认知功能的促衰老作用
- 批准号:
9882929 - 财政年份:2017
- 资助金额:
$ 36.75万 - 项目类别:
Investigating the pro-aging role of B2M and MHC molecules on regenerative and cognitive function in the brain
研究 B2M 和 MHC 分子对大脑再生和认知功能的促衰老作用
- 批准号:
10112790 - 财政年份:2017
- 资助金额:
$ 36.75万 - 项目类别:
相似海外基金
cGAS-STING Pathway Targeting Replicative Adenoviruses with CD46 Tropism and AFP Promoter Conditional Replication Restriction for the Treatment of Hepatocellular Carcinoma
cGAS-STING 通路靶向具有 CD46 趋向性和 AFP 启动子的复制腺病毒条件性复制限制用于治疗肝细胞癌
- 批准号:
10436626 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Glioma therapy with oncolytic adenoviruses and immunometabolic adjuvants
溶瘤腺病毒和免疫代谢佐剂治疗胶质瘤
- 批准号:
10557162 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Molecular therapy of replication-competent adenoviruses targeting characteristic gene mutations found in mesothelioma
针对间皮瘤中发现的特征基因突变的具有复制能力的腺病毒的分子疗法
- 批准号:
21K08199 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Glioma therapy with oncolytic adenoviruses and immunometabolic adjuvants
溶瘤腺病毒和免疫代谢佐剂治疗胶质瘤
- 批准号:
10330464 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
Structural characterization of nucleoprotein cores of human adenoviruses
人腺病毒核蛋白核心的结构表征
- 批准号:
9807741 - 财政年份:2019
- 资助金额:
$ 36.75万 - 项目类别:
Molecular biology and pathogenesis of fowl adenoviruses
禽腺病毒的分子生物学和发病机制
- 批准号:
41625-2013 - 财政年份:2018
- 资助金额:
$ 36.75万 - 项目类别:
Discovery Grants Program - Individual
The therapeutic strategies with augmented replications of oncolytic adenoviruses for malignant mesothelioma
溶瘤腺病毒增强复制治疗恶性间皮瘤的治疗策略
- 批准号:
18K15937 - 财政年份:2018
- 资助金额:
$ 36.75万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Molecular biology and pathogenesis of fowl adenoviruses
禽腺病毒的分子生物学和发病机制
- 批准号:
41625-2013 - 财政年份:2017
- 资助金额:
$ 36.75万 - 项目类别:
Discovery Grants Program - Individual
Exploring the effects of nutrient deprivation on T cells and oncolytic adenoviruses, in order to create immune activators for tumour therapy
探索营养剥夺对 T 细胞和溶瘤腺病毒的影响,以创造用于肿瘤治疗的免疫激活剂
- 批准号:
1813152 - 财政年份:2016
- 资助金额:
$ 36.75万 - 项目类别:
Studentship
Research on detection of novel adenoviruses by genetic methods
新型腺病毒的基因检测研究
- 批准号:
16K09118 - 财政年份:2016
- 资助金额:
$ 36.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)