Role of inflammation in manganese-induced neurotoxicity
炎症在锰诱导的神经毒性中的作用
基本信息
- 批准号:6478019
- 负责人:
- 金额:$ 10.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-27 至 2005-07-31
- 项目状态:已结题
- 来源:
- 关键词:basal ganglia biological signal transduction cytokine environmental contamination immunocytochemistry inflammation laboratory mouse manganese metal poisoning methylphenyltetrahydropyridine microglia neural degeneration neuroimmunomodulation neurotoxicology neurotoxins nitric oxide nitric oxide synthase substantia nigra tissue /cell culture western blottings
项目摘要
DESCRIPTION (provided by applicant)
Studies suggest that environmental contaminants, include manganese (Mn), may contribute to Idiopathic Parkinson?s Disease (IPD), but the etiology of this disease still remains elusive. Two major sources of Mn pollution in the United States arise from the reintroduction of the fuel additive methylcyclopentadienyl manganese tricarbonyl and the widespread use of
Mn-containing fungicides (maneb). Recently, the investigators obtained evidence that Mn, a neurotokicant causing Parkinson?s Disease-like symptoms, increases proinflammatory cytokines and nitric oxide production by activated microglia in vitro. These findings suggest that (i) inflammation plays a role in Mn-induced neurotoxicity, and (ii) Mn exposure may be a contributing factor (via enhanced production of inflammatory mediators) to IPD. The research proposed here will explore these possibilities utilizing both in vitro and in vivo approaches. Additional studies will begin to delineate the mechanism(s) by, which Mn enhances the inflammatory response in the brain. It is hypothesized that exposure to Mn, enhances activation of microglia which are
disproportionately distributed in the brain and as a result, over-production of proinflammatory cytokines and nitric oxide occurs with the final outcome being selective neuronal loss in the basal ganglia. Furthermore, exposure to Mn in the context of an inflammatory stimulus would potentiate the dopaminergic neuronal damage in the 1-methyl-4-phenyl-1,2,3,4- tetrahydropyridline (MPTP) mouse model of PD. Microglial cell line (N9), as well as primary microglia, will be used to determine whether Mn speciation plays a role in the increased inflammatory response. Microglial (N9)-dopaminergic (PC 12) cell line co-cultures, as well as mesencephalic primary cultures will be used in vitro studies and the effects of Mn in the presence of a microglial activator (endotoxin, LPS) on neuronal cell death will be assessed. Additionally, Mn influence on the sensitivity of the dopaminergic neurons to MPTP under the same in vitro conditions will be evaluated. C57BL/6 (MPTP-sensitive) and CD-1 (MPTP-resistant) mice will be used for in vivo studies and animals will be treated similarly to the cell cultures in the in
vitro studies. After short (14 days) exposure to Mn, some animals will be challenged with MPTP, and the degree of basal ganglia damage, as well as microglial activation will be assessed. Successful completion of the proposed research will help revealing the role of inflammation in Mn neurotoxicity and, more importantly, establish a mechanism by which environmental contaminants may contribute to the etiology of IPD. The long-term goal of the proposed
studies is to understand the role of microglia and environmental contaminants in neurodegenerative diseases.
描述(由申请人提供)
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)
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NIKOLAY M FILIPOV其他文献
NIKOLAY M FILIPOV的其他文献
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{{ truncateString('NIKOLAY M FILIPOV', 18)}}的其他基金
Mycobacterium tuberculosis-manganese interactions and neurotoxicity
结核分枝杆菌-锰的相互作用和神经毒性
- 批准号:
9018737 - 财政年份:2016
- 资助金额:
$ 10.69万 - 项目类别:
Mycobacterium tuberculosis-manganese interactions and neurotoxicity
结核分枝杆菌-锰的相互作用和神经毒性
- 批准号:
9267157 - 财政年份:2016
- 资助金额:
$ 10.69万 - 项目类别:
Role of inflammation in manganese neurotoxicity: molecular mechanisms
炎症在锰神经毒性中的作用:分子机制
- 批准号:
7735836 - 财政年份:2009
- 资助金额:
$ 10.69万 - 项目类别:
IN VIVO AND IN VITRO EFFECTS OF THE PESTICIDE ATRAZINE ON BASAL GANGLIA FUNCTION
农药阿特拉津对基底节功能的体内外影响
- 批准号:
7381806 - 财政年份:2006
- 资助金额:
$ 10.69万 - 项目类别:
EFFECTS OF PRIOR OR CONCURRENT DIELDRIN EXPOSURE ON TISSUE ATRAZINE METABOLISM
先前或同时接触狄氏剂对组织莠去津代谢的影响
- 批准号:
7381819 - 财政年份:2006
- 资助金额:
$ 10.69万 - 项目类别:
IN VIVO AND IN VITRO EFFECTS OF THE PESTICIDE ATRAZINE ON BASAL GANGLIA FUNCTION
农药阿特拉津对基底节功能的体内外影响
- 批准号:
7171027 - 财政年份:2005
- 资助金额:
$ 10.69万 - 项目类别:
PESTICIDE ATRAZINE IN BASAL GANGLIA FUNCTION
农药莠去津对基底神经节功能的影响
- 批准号:
6981710 - 财政年份:2004
- 资助金额:
$ 10.69万 - 项目类别:
Role of inflammation in manganese-induced neurotoxicity
炎症在锰诱导的神经毒性中的作用
- 批准号:
6779195 - 财政年份:2002
- 资助金额:
$ 10.69万 - 项目类别:
Role of inflammation in manganese-induced neurotoxicity
炎症在锰诱导的神经毒性中的作用
- 批准号:
6665194 - 财政年份:2002
- 资助金额:
$ 10.69万 - 项目类别:
ENVIRONMENT AFFECTS DOPAMINERGIC NEUROIMMUNE PROCESSES
环境影响多巴胺能神经免疫过程
- 批准号:
6178317 - 财政年份:2000
- 资助金额:
$ 10.69万 - 项目类别:
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