Dopamine and its metabolites in cathepsin D heterozygous mice before and after MPTP administration.
Fiche publication
Date publication
mars 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GUITTAUT Michaël
Tous les auteurs :
Crabtree D, Boyer-Guittaut M, Ouyang X, Fineberg N, Zhang J
Lien Pubmed
Résumé
Cathepsin D (CD) is a lysosomal aspartyl protease which plays an important role in alpha-synuclein degradation, and neuronal survival. CD knockout mice die by post-natal day 25+/-1 due to intestinal necrosis. We analyzed the young adult male heterozygous mice, and found no behavior abnormalities in the heterozygous mice compared to wildtype littermates. LC3-II, p62, and alpha-synuclein levels are similar, while LAMP1 is higher in the striatum in CD heterozygous compared to wildtype mice. Interestingly, we found that dopamine and metabolites in the striatum and olfactory bulbs are at higher levels than wildtype littermates, while the DOPAC/DA and HVA/DA ratio remain similar between wildtype and CD heterozygous mice. In response to sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, dopamine, DOPAC, and HVA are depleted to similar levels in the striatum in both heterozygous and wildtype mice. Dopamine synthesizing enzyme tyrosine hydroxylase, metabolic enzyme monoamine oxidase, and catechol-O-methyltransferase (COMT) levels are similar in the striatum in wildtype and heterozygous mice. These studies provide valuable information regarding how lysosomal function may contribute to neurochemical homeostasis in animal models.
Référence
Neurosci Lett. 2013 Mar 22;538:3-8