title: Peroxisome proliferator-activated receptor γ agonists accelerate oligodendrocyte maturation and influence mitochondrial functions and oscillatory Ca(2+) waves.
abstract: We have previously shown that natural (15-deoxy-Δ-prostaglandin J2) and synthetic (pioglitazone) agonists of peroxisome proliferator-activated receptor γ (PPAR-γ) strengthen the intrinsic cellular mechanisms protecting oligodendrocyte (OL) progenitors (OPs) from oxidative insults and promote their differentiation. Here, we demonstrate that repeated administrations of PPAR-γ agonists to OP cultures accelerate their differentiation to OLs, as indicated by increased numbers of O4- and O1-positive cells that show increased myelin basic protein expression, elaborated cholesterol-enrichedmembranes and have increased peroxisomes. Moreover, PPAR-γ agonist-treated OLs show increased activity of the mitochondrial respiratory chain Complex IV and an increased ability to respond to environmental signals, such as adenosine diphosphate (ADP), with oscillatory Ca waves; the latter closely correlated with the presence of mitochondria and were inhibited by the mitochondrial respiratory chain Complex I inhibitor rotenone. Because Ca oscillations and mitochondrial respiratory chain activity play crucial roles in OL differentiation, these findings suggest that PPAR-γ agonists could protect OLs and promote myelination through several mechanisms, including those involving mitochondrial functions. Our studies support the therapeutic potential of PPAR-γ agonists in brain diseases in which mitochondrial alteration, oxidative stress, and demyelination occur and point to the need for a better understanding of the role of PPAR-γ and its agonists in OL biology.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Nuccio
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bernardo
authors.forename: Roberta
authors.initials: R
authors.lastname: De Simone
authors.forename: Enrico
authors.initials: E
authors.lastname: Mancuso
authors.forename: Valerio
authors.initials: V
authors.lastname: Magnaghi
authors.forename: Sergio
authors.initials: S
authors.lastname: Visentin
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology*; D009942:Organometallic Compounds; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D016548:Prosencephalon / Q000166:cytology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D014966:Xanthenes
chemical_list: C477819:15-deoxyprostaglandin J2; D000814:Aniline Compounds; D004676:Myelin Basic Protein; D009942:Organometallic Compounds; D047495:PPAR gamma; D045162:Thiazolidinediones; D014966:Xanthenes; C110932:tetramethyl rhodamine ethyl ester; C059715:Fluo-3; D003576:Electron Transport Complex IV; D015230:Prostaglandin D2; D002118:Calcium; D000077205:Pioglitazone