Environmental neurotoxin-induced progressive model of parkinsonism in rats
| Autor: | Sarah M. Clark, Kimberly M. Valentino, Aubrey A. Siebert, Wei-Bin Shen, Carole Sztalryd, Christopher A. Shaw, Hyder A. Jinnah, Paul Yarowsky, Natalie V. Dugger, M. Samir Jafri, Paul S. Fishman, Kimberly A. McDowell |
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| Rok vydání: | 2010 |
| Předmět: |
Cycas
Male Pathology medicine.medical_specialty Flour Neurotoxins Population Physiology In Vitro Techniques Biology Rats Sprague-Dawley Parkinsonian Disorders medicine Animals Neurotoxin Amyotrophic lateral sclerosis education Parkinsonism dementia Neurons education.field_of_study Dyskinesias Plant Extracts Parkinsonism fungi Brain food and beverages biology.organism_classification medicine.disease Diet Rats Cycas micronesica Disease Models Animal Spinal Cord Neurology Nerve Degeneration Disease Progression Causal link Neurology (clinical) |
| Zdroj: | Annals of Neurology. 68:70-80 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.22018 |
| Popis: | Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex.We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism.Cycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). alpha-Synuclein (alpha-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified alpha-syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and alpha-syn aggregates in the SN.Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. |
| Databáze: | OpenAIRE |
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