Palmitoylethanolamide Protects Dentate Gyrus Granule Cells via Peroxisome Proliferator-Activated Receptor-Alpha

@article{Koch2010PalmitoylethanolamidePD,
  title={Palmitoylethanolamide Protects Dentate Gyrus Granule Cells via Peroxisome Proliferator-Activated Receptor-Alpha},
  author={Marco Koch and Susanne Kreutz and Charlotte B{\"o}ttger and Alexander H Benz and Erik Maronde and Chalid Ghadban and Horst-Werner Korf and Faramarz Dehghani},
  journal={Neurotoxicity Research},
  year={2010},
  volume={19},
  pages={330-340}
}
Endocannabinoids like 2-arachidonoylglycerol strongly modulate the complex machinery of secondary neuronal damage and are shown to improve neuronal survival after excitotoxic lesion. [] Key Result Here we show that PEA (0.001–1 μM) and the synthetic peroxisome proliferator-activated receptor (PPAR)-alpha agonist 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (Wy-14,643; 0.1–1 μM) reduced the number of microglial cells and protected dentate gyrus granule cells in excitotoxically lesioned organotypic…
Opposite Effects of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Function and Morphology of Microglia
TLDR
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TLDR
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TLDR
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TLDR
The hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective Ca2+-binding proteins (CaBPs) should be considered when analyzing the role of NAEs/PParα-signaling system in the regulation of hippocampal functions.
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TLDR
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The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells,
Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals
TLDR
It is suggested that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type) channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals.
The G Protein‐Coupled Receptor 55 Ligand l‐α‐Lysophosphatidylinositol Exerts Microglia‐Dependent Neuroprotection After Excitotoxic Lesion
TLDR
This study unmasked a yet unknown role for GPR55 in neuroprotection driven by LPI‐mediated modulation of microglia function.
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References

SHOWING 1-10 OF 61 REFERENCES
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
TLDR
Findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPar-α.
The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons.
  • S. Skaper, A. Buriani, A. Leon
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
The results suggest that non-CB1 cannabinoid receptors control, upon agonist binding, the downstream consequences of an excitotoxic stimulus and activation of such receptors may serve to downmodulate deleterious cellular processes following pathological events or noxious stimuli in both the nervous and immune systems.
Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide.
Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration
TLDR
This study identifies a cannabinoid signaling system regulating microglial cell migration and proposes that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites.
The endocannabinoid system is modulated in response to spinal cord injury in rats
2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells
TLDR
It is proposed that the endocannabinoid 2‐AG exerts its neuroprotective effects via activation of abn‐CBD‐sensitive receptors on microglial cells.
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
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