Neuroprotection and immunomodulation in the gut of parkinsonian mice with a plasmalogen precursor

Brain Res. 2019 Dec 15;1725:146460. doi: 10.1016/j.brainres.2019.146460. Epub 2019 Sep 13.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It is typically associated with motor symptoms originating from the degeneration of nigrostriatal dopamine (DA) neurons. Early stages of PD have been associated with an alteration in DA production in intestinal DAergic neurons along with inflammation. Interestingly, decreased serum concentrations of ethanolamine plasmalogens (PlsEtn) have been reported in PD patients. Ethanolamine plasmalogens play a role in vesicular fusion and release during neurotransmission, and store neuroprotective polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and are strong anti-oxidants, highlighting areas of potential therapeutic interest. Docosahexaenoic acid is known to play important roles in both the central nervous and peripheral systems, in addition to acting as a precursor of several molecules that regulate the resolution of inflammation. The present study investigated the neuroprotective and anti-inflammatory properties of the DHA-containing PlsEtn precursor, PPI-1011, in the intestine of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Treatment with PPI-1011 prevented the MPTP-induced decrease in PlsEtn levels. In addition it prevented the loss of tyrosine hydroxylase (TH) expression and reduced the infiltration of macrophages in the myenteric plexus of MPTP-treated mice. The protective effects of PPI-1011 were observed regardless of whether it was administered pre- or post- MPTP treatment. These results suggest that PPI-1011 has neuroprotective and anti-inflammatory properties in the gut and indicate its potential utility as a treatment for both early and more advanced stages of PD.

Keywords: Anti-inflammation; Dopaminergic neurons; Enteric nervous system; Neuroprotection; Parkinson’s disease; Plasmalogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Ileum / drug effects*
  • Ileum / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice, Inbred C57BL
  • Myenteric Plexus / drug effects*
  • Myenteric Plexus / immunology
  • Neurons / drug effects*
  • Neurons / immunology
  • Neuroprotective Agents / administration & dosage*
  • Parkinsonian Disorders / immunology*
  • Plasmalogens / administration & dosage*
  • Plasmalogens / blood
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Plasmalogens
  • phosphatidal ethanolamines
  • PPI-1011
  • Tyrosine 3-Monooxygenase