Dopamine and its metabolites in cathepsin D heterozygous mice before and after MPTP administration

NEUROSCIENCE LETTERS

卷:538

Article

Crabtree, Donna¹  Boyer-Guittaut, Michael^1,2,5  Ouyang, Xiaosen^1,2,3  Fineberg, Naomi⁴  Zhang, Jianhua^1,2,3 

[1] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[2] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL USA

[3] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA

[4] UAB Sch Publ Hlth, Dept Biostat, Birmingham, AL USA

[5] Univ Franche Comte, Biochim Lab, SFR IBCT,FED 4234, UFR Sci & Tech,EA3922, F-25030 Besancon, France

关键词: MPTP;    Monoamine;    Lysosome;    Heterozygotes;    Behavioral assessment;   

DOI  :  10.1016/j.neulet.2013.01.035

来源: Elsevier

【 摘 要 】

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 wild-type and heterozygous mice. These studies provide valuable information regarding how lysosomal function may contribute to neurochemical homeostasis in animal models. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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