MPTP intoxication in mice: a useful model of Leigh syndrome to study mitochondrial diseases in childhood.
Metab Brain Dis
; 24(2): 321-35, 2009 Jun.
Article
de En
| MEDLINE
| ID: mdl-19319673
ABSTRACT
The basal ganglia, which are interconnected in the striato-nigral dopaminergic network, are affected in several childhood diseases including Leigh syndrome (LS). LS is the most common mitochondrial disorder affecting children and usually arise from inhibition of the respiratory chain. This vulnerability is attributed to a particular susceptibility to energetic stress, with mitochondrial inhibition as a common pathogenic pathway. In this study we developed a LS model for neuroprotection trials in mice by using the complex I inhibitor MPTP. We first verified that MPTP significantly inhibits the mitochondrial complex I in the brain (p = 0.018). This model also reproduced the biochemical and pathological features of LS MPTP increased plasmatic lactate levels (p = 0.023) and triggered basal ganglia degeneration, as evaluated through dopamine transporter (DAT) autoradiography, tyrosine hydroxylase (TH) immunohistochemistry, and dopamine dosage. Striatal DAT levels were markedly decreased after MPTP treatment (p = 0.003). TH immunoreactivity was reduced in the striatum and substantia nigra (p = 0.005), and striatal dopamine was significantly reduced (p < 0.01). Taken together, these results confirm that acute MPTP intoxication in young mice provides a reproducible pharmacological paradigm of LS, thus opening new avenues for neuroprotection research.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie de Leigh
/
Intoxication au MPTP
/
Maladies mitochondriales
/
Complexe I de la chaîne respiratoire
/
Modèles animaux de maladie humaine
Limites:
Animals
Langue:
En
Journal:
Metab Brain Dis
Sujet du journal:
CEREBRO
/
METABOLISMO
Année:
2009
Type de document:
Article
Pays d'affiliation:
France