Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration.
Neurochem Int
; 56(2): 229-44, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19850096
ABSTRACT
Accumulated evidence has indicated that neuroinflammation is one of the important etiologic factors of Parkinson's disease (PD). Earlier studies have employed the inflammogen lipopolysaccharide (LPS) to induce inflammation of dopaminergic neurons. Methamphetamine (MA) dopaminergic toxicity similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity is frequently cited as a model of PD. In the present study, we examined whether striatal LPS exposure potentiates MA-induced dopaminergic toxicity. Combined treatment with LPS and MA significantly potentiates behavioral impairment and dopaminergic deficit. However, this combination did not significantly alter the other monoaminergic systems (e.g., serotonin, norepinephrine, and histamine). Consistently, microglial activation, labeled by F4/80 or Iba-1 in the nigrostriatal region was more pronounced with the combined treatment of LPS and MA compared to either treatment alone, but this combination did not significantly alter the microglial activation in other brain regions (e.g., hippocampus, dorsal raphe nuclei, and locus ceruleus). Furthermore, neuroinflammation, oxidative stress, and pro-apoptotic changes in the striatum were more accentuated with combined treatment of LPS and MA compared to either treatment alone. In addition, it is important that cytoplasmic accumulation of alpha-synuclein was observed in the substantia nigra of mice treated with LPS plus MA, and that L-Dopa treatment significantly attenuated behavioral changes and dopaminergic deficits induced by LPS plus MA. These results suggest that combined treatment of LPS with MA is a potential animal model for PD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
/
Corpo Estriado
/
Metanfetamina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurochem Int
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Coréia do Sul