title: Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells.
abstract: The complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical activating agent lipopolysaccharide (LPS) confers antineurogenic properties upon microglial cells. Acutely activated microglia ortheir conditioned media (CM) reduce neural stem progenitor cell (NPC) survival and prevent NPC differentiation into neurons. The present study tested the hypothesis that docosahexaenoic acid (DHA), a long-chain polyunsatured fatty acid (L-PUFA) with potent immunomodulatory properties, could dampen microglial proinflammatory functions and modulate their antineurogenic effect. We demonstrate that DHA dose dependently inhibits the synthesis of inflammatory products in activated microglia without inducing an alternative antiinflammatory phenotype. Among the possible DHA mechanisms of action, we propose the inhibition of p38 MAPK phosphorylation and the activation of the nuclear receptor peroxisome proliferator activated receptor (PPAR)-γ. The attenuation of M1 proinflammatory phenotype has relevant consequences for the survival and differentiation of NPC, because DHA reverses the antineurogenic activities of conditioned media from LPS-activated microglia. Our study identifies new relevant potentially protective and proneurogenic functions of DHA, exerted through the modulation of microglial functions, that could be exploited to sustain or promote neuroregenerative processes in damaged/aged brain.
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. mariaantonietta.ajmone-cat@iss.it
authors: Maria
authors: M
authors: Antonietta Ajmone-Cat
authors: Maria
authors: M
authors: Lavinia Salvatori
authors: Roberta
authors: R
authors: De Simone
authors: Melissa
authors: M
authors: Mancini
authors: Stefano
authors: S
authors: Biagioni
authors: Antonietta
authors: A
authors: Bernardo
authors: Emanuele
authors: E
authors: Cacci
authors: Luisa
authors: L
authors: Minghetti
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats
chemical_list: D016207:Cytokines; D004281:Docosahexaenoic Acids; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D015232:Dinoprostone