Plasmalogen precursor mitigates striatal dopamine loss in MPTP mice

Brain Res. 2017 Nov 1;1674:70-76. doi: 10.1016/j.brainres.2017.08.020. Epub 2017 Aug 19.

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.

Keywords: Dopamine; MPTP; Neuroprotection; Plasmalogen; Striatum.

MeSH terms

  • Animals
  • Biomarkers, Pharmacological / blood
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neuroprotective Agents / pharmacology
  • Parkinson Disease / metabolism
  • Plasmalogens / metabolism*
  • Plasmalogens / pharmacology
  • Serotonin / metabolism
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Biomarkers, Pharmacological
  • Dopamine Plasma Membrane Transport Proteins
  • Neuroprotective Agents
  • Plasmalogens
  • Vesicular Monoamine Transport Proteins
  • phosphatidal ethanolamines
  • Serotonin
  • Dopamine