FOREBRAIN NEUROTROPIC ABNORMALITIES & MILD COGNITIVE IMPAIRMENT IN THE ELDERLY

前脑神经营养异常

基本信息

  • 批准号:
    6299385
  • 负责人:
  • 金额:
    $ 17.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-04-15 至 2001-03-31
  • 项目状态:
    已结题

项目摘要

Although older (>65 years) individuals manifest cognitive impairments ranging from mild abnormalities to overt dementia, the molecular and cellular substrates that account for this variation remain to be defined. Several reports indicate cholinergic hypofunction in elderly humans. However, none of these studies related cholinergic changes to cognitive status. The importance of this system to human cognition is underscored by studies in Alzheimer's disease (AD) where the most consistent neurochemical abnormality to crrelate with cognitive impairment is decreases in cortical choline acetyltransferase (ChAT). Interestingly, AD patients with an increased gene dose for the apolipoprotein (ApoE) e4 allele (a genetic risk factor for AD) exhibit greater cholinergic deficts (i.e., cortical ChAT reduction and cholinergic basal forebrain(CBF) neuron loss) and are less responsive to anticholinesterase drugs. The status of the CBF system and the association of the ApoE genotype in aged individuals with mild cognitive impairment (MCI), however, is still unknown. We do know, however, that cortical ChAT levels decrease with aging in the human brain. Therefore, Specific Aim 1 will establish whether CBF degneration including reduction in cortical ChAT is associated with cognitive impairment in individuals with MCI. Findings from our group, have led to the hypothesis that the vulnerability of CBF neurons results from defects in the binding or transport of NGF and its high affinity signal transducing trkA receptor which, in turn, leads to impaired NGF trophic support in AD. Support for this suggestion is derived from our studies demonstrating that NGF protein- immunoreactivity and the message for its high affinity trkA receptors are decreased within CBF neurons whereas, cortical NGF protein is increased in AD. Taken together these observations suggest that the NGF protein accumulates within the cortex, because it is not transported in a normal fashion to CBF consumer perikarya where it is needed for its trophic effects to occur. Specific Aims 2-3 will determine whether impaired NGF transport is also associated with age-related MCI in the elderly. These studies will employ modern stereology, bioassay, immunohistochemistry and in situ hybridization procedures. The results of these investigations will have major implications for therapeutic strategies in aging and MCI and the role of genetics in considering these issues.
虽然老年人(>65岁)表现出认知障碍, 从轻微的异常到明显的痴呆, 解释这种变化的细胞基质仍有待确定。 一些报告表明老年人胆碱能功能减退。 然而,这些研究都没有将胆碱能变化与认知功能 status. 这个系统对人类认知的重要性在于 阿尔茨海默病(AD)的研究强调, 一致的神经化学异常与认知 损伤是皮质胆碱乙酰转移酶(ChAT)降低。 有趣的是,AD患者的基因剂量增加, 载脂蛋白(ApoE)e4等位基因(AD的遗传危险因素)表现出 更大的胆碱能缺陷(即,皮质ChAT减少, 胆碱能基底前脑(CBF)神经元损失)并且响应性较低 抗胆碱酯酶药物。 CBF系统的现状和 老年人ApoE基因型与轻度脑梗死的相关性 然而,认知障碍(MCI)仍然是未知的。 我们知道, 然而,在人类中,皮质ChAT水平随着年龄增长而降低 个脑袋 因此,具体目标1将确定CBF是否 包括皮质ChAT减少在内的退化与 MCI患者的认知障碍。 我们的调查结果 小组,导致了假设,CBF的脆弱性 神经元是由于NGF的结合或运输缺陷而产生的, 它的高亲和力信号转导trkA受体,反过来,导致 AD中受损的NGF营养支持。 支持这一建议的是 我们的研究表明,NGF蛋白- 免疫反应性及其高亲和力trkA受体的信息 在CBF神经元内减少,而皮质NGF蛋白在 AD增加。 这些观察结果表明, 神经生长因子蛋白质在大脑皮层内积累, 以正常方式运输到CBF消费者perikarya, 产生营养效应所必需的。 具体目标2-3将 确定受损的NGF运输是否也与 与年龄相关的MCI。 这些研究将采用现代 体视学、生物测定、免疫组织化学和原位杂交 程序. 这些调查的结果将有重大影响。 对衰老和MCI治疗策略的影响以及 遗传学在考虑这些问题。

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 }}

ELLIOTT Jay MUFSON其他文献

ELLIOTT Jay MUFSON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('ELLIOTT Jay MUFSON', 18)}}的其他基金

Default mode network dysfunction in Down Syndrome
唐氏综合症的默认模式网络功能障碍
  • 批准号:
    10635582
  • 财政年份:
    2023
  • 资助金额:
    $ 17.62万
  • 项目类别:
GALANIN REMOLDELING IN THE PROGRESSION OF AD
AD 进展过程中的甘丙肽重塑
  • 批准号:
    6927754
  • 财政年份:
    2005
  • 资助金额:
    $ 17.62万
  • 项目类别:
GALANIN REMODELING IN THE PROGRESSION OF ALZHEIMER'S DISEASE
阿尔茨海默病进展中的甘丙肽重塑
  • 批准号:
    6299298
  • 财政年份:
    2000
  • 资助金额:
    $ 17.62万
  • 项目类别:
GALANIN REMODELING IN THE PROGRESSION OF ALZHEIMER'S DISEASE
阿尔茨海默病进展中的甘丙肽重塑
  • 批准号:
    6098278
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
Basic Neuroscience Training in Age-Related Disorders
年龄相关疾病的基础神经科学培训
  • 批准号:
    8451416
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
FOREBRAIN NEUROTROPIC ABNORMALITIES & MILD COGNITIVE IMPAIRMENT IN THE ELDERLY
前脑神经营养异常
  • 批准号:
    6098740
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
Basic Neuroscience Training in Age-Related Disorders
年龄相关疾病的基础神经科学培训
  • 批准号:
    8874078
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
GALANIN REMODELING IN THE PROGRESSION OF ALZHEIMER'S DISEASE
阿尔茨海默病进展中的甘丙肽重塑
  • 批准号:
    6295529
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
Basic Neuroscience Training in Age-Related Disorders
年龄相关疾病的基础神经科学培训
  • 批准号:
    8658784
  • 财政年份:
    1999
  • 资助金额:
    $ 17.62万
  • 项目类别:
FOREBRAIN NEUROTROPIC ABNORMALITIES & MILD COGNITIVE IMPAIRMENT IN THE ELDERLY
前脑神经营养异常
  • 批准号:
    6267724
  • 财政年份:
    1998
  • 资助金额:
    $ 17.62万
  • 项目类别:

相似国自然基金

ITS-HPLC-HRMS-Bioassay多级筛选策略指导下海洋真菌中新型抗菌活性产物的发现
  • 批准号:
    41606166
  • 批准年份:
    2016
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Development of advanced bioassay analysis system for internal dose assessment
开发用于内部剂量评估的先进生物测定分析系统
  • 批准号:
    23H03142
  • 财政年份:
    2023
  • 资助金额:
    $ 17.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
This service is for The BPN Biologics program requires bioassay development expertise in order to support active cooperative agreements for drug development and discovery.
该服务适用于 BPN Biologics 计划需要生物测定开发专业知识,以支持药物开发和发现的积极合作协议。
  • 批准号:
    10949343
  • 财政年份:
    2023
  • 资助金额:
    $ 17.62万
  • 项目类别:
Development of a three-dimensional microkidney model and its disease model for bioassay
用于生物测定的三维微肾脏模型及其疾病模型的开发
  • 批准号:
    23H01983
  • 财政年份:
    2023
  • 资助金额:
    $ 17.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
BIOASSAY SME CONSULTING SERVICES
生物测定中小企业咨询服务
  • 批准号:
    10837635
  • 财政年份:
    2022
  • 资助金额:
    $ 17.62万
  • 项目类别:
Development of a qualified pharmacokinetic bioassay to support preclinical and clinical studies of MM-008, a non-hormonal contraceptive antibody
开发合格的药代动力学生物测定法以支持非激素避孕抗体 MM-008 的临床前和临床研究
  • 批准号:
    10459074
  • 财政年份:
    2022
  • 资助金额:
    $ 17.62万
  • 项目类别:
BIOASSAY SME CONSULTING SERVICES
生物测定中小企业咨询服务
  • 批准号:
    10721007
  • 财政年份:
    2022
  • 资助金额:
    $ 17.62万
  • 项目类别:
Development of rapid and sensitive bioassay methods to contribute to actinide internal exposure medical response
开发快速、灵敏的生物测定方法,有助于锕系元素内照射医疗反应
  • 批准号:
    22K12384
  • 财政年份:
    2022
  • 资助金额:
    $ 17.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
BIOASSAY SME CONSULTING SERVICES
生物测定中小企业咨询服务
  • 批准号:
    10721008
  • 财政年份:
    2022
  • 资助金额:
    $ 17.62万
  • 项目类别:
Development of simple bioassay for detection of environmental trace contaminants and demonstration in Asian countries
开发用于检测环境痕量污染物的简单生物测定法并在亚洲国家进行示范
  • 批准号:
    21H01577
  • 财政年份:
    2021
  • 资助金额:
    $ 17.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
L2M Market Assessment Grant: a bioassay to predict birth timing.
L2M 市场评估补助金:预测出生时间的生物测定。
  • 批准号:
    571251-2022
  • 财政年份:
    2021
  • 资助金额:
    $ 17.62万
  • 项目类别:
    Idea to Innovation
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了