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Molecular Neurobiology

, Volume 55, Issue 11, pp 8455–8472 | Cite as

N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice

  • Rosalia Crupi
  • Daniela Impellizzeri
  • Marika Cordaro
  • Rosalba Siracusa
  • Giovanna Casili
  • Maurizio Evangelista
  • Salvatore Cuzzocrea
Article

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD induced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model. Male CD mice (21 months of age) were pre-treated for 60 days with PEAm. After this time, they received four intraperitoneal injections of MPTP over a 24-h period and were killed 7 days later. On the 8th day, brains were processed. Pretreatment with PEAm ameliorated behavioral deficits and the reductions in expression of tyrosine hydroxylase and dopamine transporter, while blunting the upregulation of α-synuclein and β3-tubulin in the substantia nigra after MPTP induction. Moreover, PEAm reduced proinflammatory cytokine expression and showed a pro-neurogenic effect in hippocampus. These findings propose this strategy as a valid approach to prevent neurodegenerative diseases associated with old age.

Keywords

Age Mice Neuroinflammation Palmitoylethanolamide Parkinson’s disease 

Notes

Acknowledgments

The authors would like to thank Mr. Soraci Francesco for secretarial and administrative assistance, Medici Maria Antonietta for excellent technical assistance, and Miss Malvagni Valentina for editorial support with the manuscript.

Compliance with Ethical Standards

Disclosure Statement

Salvatore Cuzzocrea is co-inventor on patent WO2013121449 A8 (Epitech Group Srl) which deals with methods and compositions for the modulation of amidases capable of hydrolysing N-acylethanolamines employable in the treatment of inflammatory diseases. This invention is wholly unrelated to the present study. Moreover, Prof. Cuzzocrea is also, with Epitech Group, a co-inventor on the following patent: EP 2821083; MI2014 A001495; 102015000067344 that are however unrelated to the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Chemical, Biological, Pharmacological and Environmental SciencesUniversity of MessinaMessinaItaly
  2. 2.Institute of Anaesthesiology and ReanimationCatholic University of the Sacred HeartRomeItaly
  3. 3.Department of Pharmacological and Physiological ScienceSaint Louis UniversitySaint LouisUSA

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