Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation.
BMC Neurosci
; 19(1): 77, 2018 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-30497382
ABSTRACT
BACKGROUND:
The treatment of Parkinson's disease is often complicated by levodopa-induced dyskinesia (LID). Nicotinic acetylcholine receptor agonists can alleviate LID in animal models but may be less effective in conditions of severe dopaminergic denervation. While the mechanisms of LID remain incompletely understood, elevated corticostriatal levels of the brain-derived neurotrophic factor (BDNF) have been suggested to play a role. Here, female mice with near-total unilateral 6-hydroxydopamine-induced nigrostriatal lesions were chronically treated with levodopa, and the effects of the α7 nicotinic receptor partial agonist AZD0328 and nicotine on LID were assessed. At the end of the experiment, BDNF protein levels in the prefrontal cortex and striatum were measured.RESULTS:
Five-day treatments with three escalating doses of AZD0328 and a 10-week treatment with nicotine failed to alleviate LID. BDNF levels in the lesioned striatum correlated positively with LID severity, but no evidence was found for a levodopa-induced elevation of corticostriatal BDNF in the lesioned hemisphere. The nicotine treatment decreased BDNF levels in the prefrontal cortex but had no effect on striatal BDNF.CONCLUSIONS:
The findings suggest that treatment of LID with nicotinic agonists may lose its effectiveness as the disease progresses, represent further evidence for a role for BDNF in LID, and expand previous knowledge on the effects of long-term nicotine treatment on BDNF.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopaminérgicos
/
Agonistas Nicotínicos
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Fator Neurotrófico Derivado do Encéfalo
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Transtornos Parkinsonianos
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Discinesia Induzida por Medicamentos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article