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

Collapse Box

Abstract

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

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.