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Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Mar 17; Vol. 22 (6). Date of Electronic Publication: 2021 Mar 17. - Publication Year :
- 2021
-
Abstract
- Palmitoylethanolamide (PEA) is an endogenous lipid produced on demand by neurons and glial cells that displays neuroprotective properties. It is well known that inflammation and neuronal damage are strictly related processes and that microglia play a pivotal role in their regulation. The aim of the present work was to assess whether PEA could exert its neuroprotective and anti-inflammatory effects through the modulation of microglia reactive phenotypes. In N9 microglial cells, the pre-incubation with PEA blunted the increase of M1 pro-inflammatory markers induced by lipopolysaccharide (LPS), concomitantly increasing those M2 anti-inflammatory markers. Images of microglial cells were processed to obtain a set of morphological parameters that highlighted the ability of PEA to inhibit the LPS-induced M1 polarization and suggested that PEA might induce the anti-inflammatory M2a phenotype. Functionally, PEA prevented Ca <superscript>2+</superscript> transients in both N9 cells and primary microglia and antagonized the neuronal hyperexcitability induced by LPS, as revealed by multi-electrode array (MEA) measurements on primary cortical cultures of neurons, microglia, and astrocyte. Finally, the investigation of the molecular pathway indicated that PEA effects are not mediated by toll-like receptor 4 (TLR4); on the contrary, a partial involvement of cannabinoid type 2 receptor (CB2R) was shown by using a selective receptor inverse agonist.
- Subjects :
- Adenosine Triphosphate pharmacology
Animals
Calcium metabolism
Cell Polarity drug effects
Cells, Cultured
Cytokines metabolism
Humans
Inflammation Mediators metabolism
Lipopolysaccharides pharmacology
Mice
Microglia drug effects
NF-kappa B metabolism
Rats
Receptor, Cannabinoid, CB2 metabolism
THP-1 Cells
Tetradecanoylphorbol Acetate pharmacology
Toll-Like Receptor 4 metabolism
Tumor Necrosis Factor-alpha metabolism
Amides pharmacology
Ethanolamines pharmacology
Microglia metabolism
Neuroprotective Agents pharmacology
Palmitic Acids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33802689
- Full Text :
- https://doi.org/10.3390/ijms22063054