Role of Environment in Neuroprotection

环境在神经保护中的作用

• 批准号: 6783811
• 负责人: RICHARD J SMEYNE
• 金额: $ 19.47万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783811
• 关键词: Parkinson' s disease; behavioral /social science research tag; brain derived neurotrophic factor; disease /disorder model; disease /disorder prevention /control; exercise; laboratory mouse; methylphenyltetrahydropyridine; neurotoxins; socioenvironment

DESCRIPTION (provided by applicant): PD is a debilitating neurological disorder that strikes 20 per 100,000 persons greater than 50 years of age. The cause of >90% of all PD cases are unknown. However, the discovery of the meperidine by-product 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has provided a useful model of Parkinsonism that appears to recapitulate the pathology of the disease seen in man. Exposure to this prototypical "environmental toxin" causes a selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). MPTP is a lipophillic molecule that rapidly enters the brain and is metabolized to MPP+ through a series of intermediates to MPP+ by the enzyme MAO-B. MPP + is a substrate for dopamine uptake mechanisms and it accumulates intraneuronally and interferes with complex I of the electron transport chain. We have recently shown that the glial cell is the critical cell for conferring protection or susceptibility to this toxin. Since PD is progressive, both in terms of cell loss and symptomotology, it would be of tremendous clinical value if there were cell biological, pharmacological or non-pharmacological methods that could attenuate cell loss; with or without interruption of the disease triggers. Alternatively, at the least, it would be important to slow the progression of cell loss once symptoms arose. There is a significant literature, dating back to the late 1700's that altering an animals' environment can lead to neurological changes. These changes are manifested as increased brain size, increased learning, and recently it has been shown that environment can increase neurogenesis. Recently, we have preliminary data to suggest that mice raised in an "Enriched Environment" (EE) are protected from MPTP toxicity. In this application, we will study and further establish the EE model. In addition, we will examine if the components (exercise, alterations in environmental complexity and/or social interactions) of the EE can confer neuroprotection. In addition, we will examine the role of the neurotrophin BDNF in EE-dependent neuroprotection. The work proposed and subsequent results generated in the application will be used as pilot data. We believe that the EE model may provide a new approach to prevention of PD symptomatology as well as other neurodegenerative disorders.

描述（由申请人提供）：