title: Dopamine and its metabolites in cathepsin D heterozygous mice before and after MPTP administration.
abstract: Cathepsin D (CD) is a lysosomal aspartyl protease which plays an important role in α-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 α-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.
authors: Department of Pathology, University of Alabama at Birmingham, AL 35294, USA.
authors: Donna
authors: D
authors: Crabtree
authors: Michaël
authors: M
authors: Boyer-Guittaut
authors: Xiaosen
authors: X
authors: Ouyang
authors: Naomi
authors: N
authors: Fineberg
authors: Jianhua
authors: J
authors: Zhang
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006579:Heterozygote; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D002402:Cathepsin D; D004298:Dopamine; D006719:Homovanillic Acid
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