Dramatic differences in susceptibility to l-DOPA-induced dyskinesia between mice that are aged before or after a nigrostriatal dopamine lesion
| Autor: | Angela Cenci Nilsson, Veronica Francardo, Francesco Bez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Dyskinesia Drug-Induced medicine.medical_specialty Parkinson's disease Apomorphine Mouse Dopamine Nigrostriatal pathway Motor Activity Serotonergic lcsh:RC321-571 Levodopa Lesion 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Oxidopamine lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Dopaminergic Parkinson Disease medicine.disease Corpus Striatum Mice Inbred C57BL Disease Models Animal Ageing 030104 developmental biology Endocrinology medicine.anatomical_structure Neurology Dyskinesia Anesthesia Neuroplasticity medicine.symptom Psychology 6-Hydroxydopamine 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurobiology of Disease, Vol 94, Iss, Pp 213-225 (2016) |
| Popis: | Mice with striatal 6-hydroxydopamine (6-OHDA) lesions are widely used as a model to study the effects of neurorestorative, symptomatic, or antidyskinetic treatments for Parkinson's disease (PD). The standard praxis is to utilize young adult mice with relatively acute 6-OHDA lesions. However, long post-lesion intervals may be required for longitudinal studies of treatment interventions, and the long-term stability of the model's behavioral and cellular phenotypes is currently unknown. In this study, C57Bl/6J mice sustained unilateral striatal 6-OHDA lesions at approx. 2 months of age, and were allowed to survive for 1, 10 or 22 months. Another group of mice sustained the lesion at the age of 23 months and survived for one month thereafter. Baseline and drug-induced motor behaviors were examined using a battery of tests (utilizing also a novel video-based methodology). The extent of nigral dopamine cell loss was stable across post-lesion intervals and ages. However, a prominent sprouting of both dopaminergic and serotonergic fibers was detected in the caudate-putamen in animals that survived until 10 and 22 months post-lesion. This phenomenon was associated with a recovery of baseline motor deficits, and with a lack of dyskinetic responses upon treatment with either L-DOPA or apomorphine. By contrast, mice sustaining the lesion at 23 months of age showed a striking susceptibility to the dyskinetic effects of both L-DOPA and apomorphine, which was associated with a pronounced drug-induced upregulation of ∆FosB in the ventrolateral striatum. The results reveal a remarkable compensatory capacity of a damaged nigrostriatal pathway in ageing mice, and how this impacts on the response to dopaminergic therapies for PD. (Less) |
| Databáze: | OpenAIRE |
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