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Time-lines of neural degeneration in ALS-PDC mouse model

ALS-PDC 小鼠模型神经退行性变的时间线

基本信息

批准号：
7750493
负责人：
CHRISTOPHER Ariel SHAW
金额：
$ 20.76万
依托单位：
UNIVERSITY OF BRITISH COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-15 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7750493
关键词：
Address Adolescent Adult Affect Age Astrocytes Behavioral Biochemical Biological Assay Biological Markers Cell Death Cellular Stress Cognitive Complex Cycad Data Dementia Dependence Development Diet Disease Disease model Early treatment Etiology Event Exposure to Flour Functional disorder Future Generations Genetic Genetic Predisposition to Disease Glucosides Goals Hippocampus (Brain)Human In Vitro Laboratories Life Longevity Modeling Motor Mus Nerve Degeneration Nervous system structure Neurodegenerative Disorders Neurons Neurotoxins Onset of illness Outcome Parkinsonian Disorders Pathway interactions Phase Phosphoric Monoester Hydrolases Play Predisposition Preparation Process Prophylactic treatment Protein Kinase Proteins Protocols documentation Recovery Recovery of Function Research Research Personnel Role Seeds Sensory Series Severities Sitosterol Sitosterols Slice Spinal Cord Staging Susceptibility Gene Testing Therapeutic Intervention Time TimeLine Toxic Actions Toxic Environmental Substances Toxic effect Toxin Twin Multiple Birth Variant Water Work age effect age related base behavior test behavioral health design feeding human disease in vivo indexing insight interest male mouse model nervous system disorder neuropathology neurotoxicity novel postnatal prevent programs prophylactic relating to nervous system research study sterol glucoside therapeutic target tissue culture treatment strategy

项目摘要

ALS parkinsonism-dementia complex (ALS-PDC) is a neurological disease that can present as classical ALS, an Alzeheimer's-like disorder with associated parkinsonism features, or a combination. It is a cluster of age-dependent neurodegenerative disorders, representing the only widely acknowledged such cluster and may offer vital clues to the etiology of related disorders. We have successfully modeled the disease by feeding washed cycad flour to adult mice, which develop behavioral and histopathological deficits resembling ALS-PDC. The ability to model the disease allows us to ask fundamental questions of great potential impact for related disorders: Which environmental toxins and genetic susceptibilities contribute to neurodegeneration? What is the time course of the behavioral and pathological deficits from initial expo- sure until behavioral end state? How does age affect disease development and progression? Finally, based on the above, can we design prophylactic and early treatment strategies to prevent further neurode- generation? Using our model of ALS-PDC, we will address the crucial questions of (1) neurodegeneration time-line and (2) the impact of neurotoxins as a function of age. To probe these questions, adult male CD-1 mice will be fed washed cycad or the isolated putative cycad toxins, variant steryl glucosides. A detailed time-line of behavioral, morphological, and biochemical events will be studied from initial exposure through to an end state for both groups. To further examine crucial events in the neurodegeneration cascade, neural cells will be examined in a tissue culture preparation during and following exposure to steryl glucosides. The proposed age effects study will examine two aspects: cycad neurotoxin-induced behavioral and pathological effects as a function of age over a span of 1 to 18 months. In a second series of experiments, we will determine if an early exposure to cycad toxins can exacerbate a late adult expo- sure. These data will provide therapeutic targets to prevent or halt the progression of neurodegeneration.

ALS帕金森-痴呆复合体（ALS- pdc）是一种典型的神经系统疾病