Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum

Neuropharmacology. 2019 Mar 1;146:184-197. doi: 10.1016/j.neuropharm.2018.11.037. Epub 2018 Nov 26.

Abstract

Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3 ± 1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPARα-immunoreactive neurons in the striatum. Ethanol-related neurobiological alterations such as a reduction in the number of microglial cells expressing iNOS (a cytokine-inducible immune defense) and in adult neural stem/progenitor cell (NSPC) proliferation (phospho-H3 and BrdU) and maturation (BrdU/β3-tubulin), as well as an increase in damage cell activity (FosB) and apoptosis (cleaved caspase 3) were also observed in the rat striatum. Pharmacological administration of OEA (10 mg/kg) for 5 days during ethanol exposure exacerbated ethanol-induced hypolocomotion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPARα-positive cell population and NSPC proliferation and maturation. OEA also decreased astrocyte-related vimentin immunoreactivity and increased microglial cell population (Iba-1, iNOS) in the striatum. These results suggest that OEA-PPARα signaling modulates glial activation, cell apoptosis and NSPC proliferation and maturation in response to striatal-specific neurobiological alterations induced by prolonged ethanol intake in rats.

Keywords: Alcohol; Locomotion; Microglia; Neurogenesis; PPARα; Striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alcohol Drinking / drug therapy
  • Amidohydrolases / blood
  • Animals
  • Apoptosis / drug effects
  • Arachidonic Acids / pharmacology
  • Aspartate Aminotransferases / blood
  • Calcium-Binding Proteins / metabolism
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Endocannabinoids / pharmacology*
  • Ethanol / pharmacology*
  • Ethanolamines / analysis
  • Ethanolamines / blood
  • Glial Fibrillary Acidic Protein / metabolism
  • Hepatobiliary Elimination
  • Locomotion / drug effects
  • Male
  • Microfilament Proteins / metabolism
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Neostriatum / drug effects*
  • Neostriatum / metabolism*
  • Neurons / drug effects
  • Oleic Acids / pharmacology*
  • PPAR alpha / metabolism
  • Phospholipase D / blood
  • Polyunsaturated Alkamides / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • gamma-Glutamyltransferase / blood

Substances

  • Aif1 protein, rat
  • Arachidonic Acids
  • Calcium-Binding Proteins
  • Endocannabinoids
  • Ethanolamines
  • Fosb protein, rat
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • N-acylethanolamines
  • Oleic Acids
  • PPAR alpha
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-fos
  • oleoylethanolamide
  • Ethanol
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Napepld protein, rat
  • Phospholipase D
  • Caspase 3
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide