Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility
| Autor: | David A. Greenberg, Allyn Franklin, Nephi Stella, Sophie Parmentier-Batteur, Lisa Walter |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cannabinoid receptor
Polyunsaturated Alkamides medicine.medical_treatment Receptors Drug Development/Plasticity/Repair Motility Arachidonic Acids Palmitic Acids Biology Nitric Oxide Brain Ischemia Cell Line Glycerides chemistry.chemical_compound Mice Phagocytosis Cell Movement Cannabinoid Receptor Modulators medicine Animals Receptor Receptors Cannabinoid Neuroinflammation Cerebral Cortex Palmitoylethanolamide Cannabinoids General Neuroscience food and beverages Endocannabinoid system Amides Heterotrimeric GTP-Binding Proteins Microglial cell migration chemistry Ethanolamines Fatty Acids Unsaturated lipids (amino acids peptides and proteins) Cannabinoid Microglia Neuroscience Cell Division Endocannabinoids |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| ISSN: | 1529-2401 |
| Popis: | Focal cerebral ischemia (FCI) induces rapid neuronal death in the ischemic core, which gradually expands toward the penumbra, partly as the result of a neuroinflammatory response. It is known that propagation of neuroinflammation involves microglial cells, the resident macrophages of the brain, which are highly motile when activated by specific signals. However, the signals that increase microglial cell motility in response to FCI remain mostly elusive.Here, we tested the hypothesis that endocannabinoids mediate neuroinflammation propagation by increasing microglial cell motility. We found that, in mouse cerebral cortex, FCI greatly increases palmitoylethanolamide (PEA), only moderately increases anandamide [arachidonylethanolamide (AEA)], and does not affect 2-arachidonoylglycerol levels. We also found that PEA potentiates AEA-induced microglial cell migration, without affecting other steps of microglial activation, such as proliferation, particle engulfment, and nitric oxide production. This potentiation of microglial cell migration by PEA involves reduction in cAMP levels. In line with this, we provide evidence that PEA acts through Gi/o-coupled receptors. Interestingly, these receptors engaged by PEA are pharmacologically distinct from CB1and CB2cannabinoid receptors, as well as from the WIN and abn-CBD (abnormal-cannabidiol) receptors, two recently identified cannabinoid receptors.Our results show that PEA and AEA increase after FCI and synergistically enhance microglial cell motility. Because such a response could participate in the propagation of the FCI-induced neuroinflammation within the CNS, and because PEA is likely to act through its own receptor, a better understanding of the receptor engaged by PEA may help guide the search for improved therapies against neuroinflammation. |
| Databáze: | OpenAIRE |
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