Behavioral, Neurochemical and Histological Alterations Promoted by Bilateral Intranigral Rotenone Administration: A New Approach for an Old Neurotoxin
| Autor: | Camila Guimarães Moreira, Patrícia A. Dombrowski, Pamela Sabioni, Mariza Bortolanza, Marcelo M.S. Lima, Claudio Da Cunha, Maria A.B.F. Vital, Janaína K. Barbiero, Deborah Ariza |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Serotonin Parkinson's disease Microinjections Tyrosine 3-Monooxygenase Substantia nigra Motor Activity Pharmacology Toxicology chemistry.chemical_compound Neurochemical Parkinsonian Disorders Dopamine Rotenone Avoidance Learning Animals Medicine Rats Wistar Tyrosine hydroxylase Uncoupling Agents business.industry Pars compacta Dopaminergic Neurons General Neuroscience Dopaminergic Hydroxyindoleacetic Acid medicine.disease Rats Substantia Nigra Disease Models Animal chemistry Nerve Degeneration Exploratory Behavior business Neuroscience Serotonergic Neurons medicine.drug |
| Zdroj: | Neurotoxicity Research. 21:291-301 |
| ISSN: | 1476-3524 1029-8428 |
| DOI: | 10.1007/s12640-011-9278-3 |
| Popis: | Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson's disease (PD). In order to counteract these limitations, this study characterized a precise neurotoxin-delivery strategy employing the bilateral intranigral administration protocol of rotenone as a reliable model of PD. We performed bilateral intranigral injections of rotenone (12 μg) and subsequent general activity (1, 10, 20, and 30 days after rotenone) and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by neurochemical and immunohistochemical tests. We have observed that rotenone was able to produce a remarkable reduction on the percentage of tyrosine hydroxylase immunoreactive neurons (about 60%) within the substantia nigra pars compacta. Dopamine (DA) was severely depleted at 30 days after rotenone administration, similarly to its metabolites. In addition, an increase in DA turnover was detected at the same time-point. In parallel, striatal serotonin and its metabolite were found to be increased 30 days after the neurotoxic insult, without apparent modification in the serotonin turnover. Besides, motor behavior was impaired, mainly 1 day after rotenone. Furthermore, learning and memory processes were severely disrupted in different time-points, particularly at the training and test session (30 days). We now provide further evidence of a time-dependent neurodegeneration associated to cognitive impairment after the single bilateral intranigral administration of rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD. |
| Databáze: | OpenAIRE |
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