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Plasmalogen precursor mitigates striatal dopamine loss in MPTP mice
- Source :
- Brain Research. 1674:70-76
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 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.
- Subjects :
- Male
0301 basic medicine
Serotonin
medicine.medical_specialty
Plasmalogen
Dopamine
Plasmalogens
Vesicular monoamine transporter 2
Neuroprotection
Biomarkers, Pharmacological
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Molecular Biology
Dopamine Plasma Membrane Transport Proteins
biology
Chemistry
General Neuroscience
MPTP
Parkinson Disease
Corpus Striatum
Mice, Inbred C57BL
Neostriatum
Neuroprotective Agents
030104 developmental biology
Endocrinology
Biochemistry
Docosahexaenoic acid
Vesicular Monoamine Transport Proteins
Toxicity
biology.protein
Neurology (clinical)
030217 neurology & neurosurgery
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1674
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....4398f77d76f9adedfd5456dabc223d26