[en] Cerebral inflammatory events play an important part in the pathogenesis of Alzheimer's disease (AD). Agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that mediates anti-inflammatory actions of non-steroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones, have been therefore proposed as a potential treatment of AD. Experimental evidence suggests that cortical noradrenaline (NA) depletion due to degeneration of the locus ceruleus (LC) - a pathological hallmark of AD - plays a permissive role in the development of inflammation in AD. To study a possible relationship between NA depletion and PPARgamma-mediated suppression of inflammation we investigated the influence of NA on PPARgamma expression in murine primary cortical astrocytes and neurons. Incubation of astrocytes and neurons with 100 micro m NA resulted in an increase of PPARgamma mRNA as well as PPARgamma protein levels in both cell types. These effects were blocked by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phentolamine, suggesting that they might be mediated by beta-adrenergic receptors. Our results indicate for the first time that PPARgamma expression can be modulated by the cAMP signalling pathway, and suggest that the anti-inflammatory effects of NA on brain cells may be partly mediated by increasing PPARgamma levels. Conversely, decreased NA due to LC cell death in AD may reduce endogenous PPARgamma expression and therefore potentiate neuroinflammatory processes.
Disciplines :
Neurology
Author, co-author :
Klotz, Luisa; Department of Neurology, University of Bonn, Bonn, Germany
Sastre, Magdalena; Department of Neurology, University of Bonn, Bonn, Germany
Kreutz, Anne; Department of Neurology, University of Bonn, Bonn, Germany
Gavrilyuk, Vitaliy; Department of Anesthesiology, University of Illinois, Chicago, IL, United States
Klockgether, Thomas; Department of Neurology, University of Bonn, Bonn, Germany
Feinstein, Douglas L; Department of Anesthesiology, University of Illinois, Chicago, IL, United States
HENEKA, Michael ; Department of Neurology, University of Bonn, Bonn, Germany ; Department of Neurology, Neuroinflammation Research Group, 53127 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Noradrenaline induces expression of peroxisome proliferator activated receptor gamma (PPARgamma) in murine primary astrocytes and neurons.
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