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Plasmalogen precursor mitigates striatal dopamine loss in MPTP mice.
- Source :
-
Brain research [Brain Res] 2017 Nov 01; Vol. 1674, pp. 70-76. Date of Electronic Publication: 2017 Aug 19. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Biomarkers, Pharmacological blood
Corpus Striatum metabolism
Dopamine Plasma Membrane Transport Proteins metabolism
Male
Mice
Mice, Inbred C57BL
Neostriatum drug effects
Neostriatum metabolism
Neuroprotective Agents pharmacology
Parkinson Disease metabolism
Plasmalogens pharmacology
Serotonin metabolism
Vesicular Monoamine Transport Proteins metabolism
Corpus Striatum drug effects
Dopamine metabolism
Plasmalogens metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1674
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 28830769
- Full Text :
- https://doi.org/10.1016/j.brainres.2017.08.020