title: Microglial polarization and plasticity: evidence from organotypic hippocampal slice cultures.
abstract: Increasing evidence indicates that "functional plasticity" is not solely a neuronal attribute but a hallmark of microglial cells, the main brain resident macrophage population. Far from being a univocal phenomenon, microglial activation can originate a plethora of functional phenotypes, encompassing the classic M1 proinflammatory and the alternative M2 anti-inflammatory phenotypes. This concept overturns the popular view of microglial activation as a synonym of neurotoxicity and neurogenesis failure in brain disorders. The characterization of the alternative programs is a matter of intense investigation, but still scarce information is available on the course of microglial activation, on the reversibility of the different commitments and on the capability of preserving molecular memory of previous priming stimuli. By using organotypic hippocampal slice cultures as a model, we developed paradigms of stimulation aimed at shedding light on some of these aspects. We show that persistent stimulation of TLR4 signaling promotes an anti-inflammatory response and microglial polarization toward M2-like phenotype. Moreover, acute and chronic preconditioning regimens permanently affect the capability to respond to a later challenge, suggesting the onset of mechanisms of molecular memory. Similar phenomena could occur in the intact brain and differently affect the vulnerability of mature and newborn neurons to noxious signals.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00185 Rome, Italy. mariaantonietta.ajmone-cat@iss.it
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Ajmone-Cat
authors.forename: Melissa
authors.initials: M
authors.lastname: Mancini
authors.forename: Roberta
authors.initials: R
authors.lastname: De Simone
authors.forename: Piera
authors.initials: P
authors.lastname: Cilli
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000166:cytology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001119:Arginase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines; D015232:Dinoprostone; D007334:Insulin-Like Growth Factor I; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C581013:MRC1 protein, mouse; C519530:insulin-like growth factor-1, mouse; C077623:Ptgs2 protein, mouse; C496512:Ptgs1 protein, mouse; C544448:Arg1 protein, mouse
keywords: M1; M2 inflammation; brain macrophages; endotoxin tolerance; microglia