title: Plasmalogen Augmentation Reverses Striatal Dopamine Loss in MPTP Mice.
abstract: Plasmalogens are a class of glycerophospholipids shown to play critical roles in membrane structure and function. Decreased plasmalogens are reported in the brain and blood of Parkinson's disease (PD) patients. The present study investigated the hypothesis that augmenting plasmalogens could protect striatal dopamine neurons that degenerate in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice, a PD model. First, in a pre-treatment experiment male mice were treated for 10 days with the docosahexaenoic acid (DHA)-plasmalogen precursor PPI-1011 (10, 50 and 200 mg/kg). On day 5 mice received MPTP and were killed on day 11. Next, in a post-treatment study, male mice were treated with MPTP and then received daily for 5 days PPI-1011 (5, 10 and 50 mg/kg). MPTP treatment reduced serum plasmalogen levels, striatal contents of dopamine (DA) and its metabolites, serotonin, DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). Pre-treatment with PPI-1011 (10 and 50 mg/kg) prevented all MPTP-induced effects. Positive correlations were measured between striatal DA contents and serum plasmalogen levels as well as striatal DAT and VMAT2 specific binding. Post-treatment with PPI-1011 prevented all MPTP-induced effects at 50 mg/kg but not at lower doses. Positive correlations were measured between striatal DA contents and serum plasmalogen levels as well as striatal DAT and VMAT2 specific binding in the post-treatment experiment. PPI-1011 treatment (10 days at 5, 10 and 50 mg/kg) of intact mice left unchanged striatal biogenic amine contents. These data demonstrate that treatment with a plasmalogen precursor is capable of protecting striatal dopamine markers in an animal model of PD.
authors.affiliation: Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, Quebec City, Canada.|Faculty of Pharmacy, Laval University, Quebec City, Canada.
authors.forename: Edith
authors.initials: E
authors.lastname: Miville-Godbout
authors.affiliation: Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, Quebec City, Canada.|Faculty of Pharmacy, Laval University, Quebec City, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bourque
authors.affiliation: Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, Quebec City, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.affiliation: Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, Quebec City, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Al-Sweidi
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.
authors.forename: Tara
authors.initials: T
authors.lastname: Smith
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.|Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Mochizuki
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.
authors.forename: Vijitha
authors.initials: V
authors.lastname: Senanayake
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.
authors.forename: Dushmanthi
authors.initials: D
authors.lastname: Jayasinghe
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Phenomenome Discoveries Inc., Saskatoon, Canada.
authors.forename: Dayan
authors.initials: D
authors.lastname: Goodenowe
authors.affiliation: Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, Quebec City, Canada.|Faculty of Pharmacy, Laval University, Quebec City, Canada.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000209:etiology / Q000517:prevention & control*; D010955:Plasmalogens / Q000627:therapeutic use*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D010955:Plasmalogens; D050493:Vesicular Monoamine Transport Proteins; D004281:Docosahexaenoic Acids; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine