Skip Navigation LinksHome > October 2011 - Volume 70 - Issue 10 > Peroxisome Proliferator-Activated Receptor γ Agonists Accele...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e3182309ab1
Original Articles

Peroxisome Proliferator-Activated Receptor γ Agonists Accelerate Oligodendrocyte Maturation and Influence Mitochondrial Functions and Oscillatory Ca2+ Waves

De Nuccio, Chiara PhD; Bernardo, Antonietta PhD; De Simone, Roberta DSc; Mancuso, Enrico DSc; Magnaghi, Valerio PhD; Visentin, Sergio DSc; Minghetti, Luisa PhD

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We have previously shown that natural (15-deoxy-Δ12,14-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 Ca2+ waves; the latter closely correlated with the presence of mitochondria and were inhibited by the mitochondrial respiratory chain Complex I inhibitor rotenone. Because Ca2+ 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.

© 2011 American Association of Neuropathologists, Inc


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