Plasmalogen precursor mitigates striatal dopamine loss in MPTP mice.
Ethanolamine plasmalogens (PlsEtn) are a class of glycerophospholipids characterized by a vinyl-ether bond at the sn-1 position that play an important role in the structure and function of membranes. Previous reports have suggested a link between reduced blood and brain PlsEtn levels and Parkinson's disease (PD). We recently reported that the DHA containing plasmalogen precursor PPI-1011 protected striatal dopamine (DA) against MPTP toxicity in mice. In this paper, we further investigate the specificity requirements of the lipid side chains by testing the oleic acid-containing plasmalogen precursor PPI-1025. Male mice were treated for 10days with daily oral administration of PPI-1025 (10, 50 or 200mg/kg). On day 5 mice received MPTP and were sacrificed on Day 11. Treatment with PPI-1025 prevented MPTP-induced decrease of DA and serotonin, as well as their metabolites. In addition, PPI-1025 treatment prevented the MPTP-induced decrease of the striatal dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) specific binding. Significant positive correlations were measured between striatal DA concentrations and DAT or VMAT2 specific binding, as well as with serum plasmalogen concentrations. The neuroprotective effect of PPI-1025 displayed a bell-curve dose-dependency losing effect at the highest dose tested. The similar protective response of oleic and docosahexaenoic acid (DHA)-containing plasmalogen precursors suggests that the neuroprotection observed is not only due to DHA but to the oleic substituent and the plasmalogen backbone.
['Miville-Godbout|Edith|E|', 'Bourque|Mélanie|M|', 'Morissette|Marc|M|', 'Al-Sweidi|Sara|S|', 'Smith|Tara|T|', 'Jayasinghe|Dushmanthi|D|', 'Ritchie|Shawn|S|', 'Di Paolo|Thérèse|T|']
D000818:Animals D054316:Biomarkers, Pharmacological D003342:Corpus Striatum D004298:Dopamine D050483:Dopamine Plasma Membrane Transport Proteins D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D017072:Neostriatum D018696:Neuroprotective Agents D010300:Parkinson Disease D010955:Plasmalogens D012701:Serotonin D050493:Vesicular Monoamine Transport Proteins
Plasmalogen Dopamine MPTP Neuroprotection Striatum