Noradrenaline induces expression of peroxisome proliferator activated receptor gamma (PPARγ) in murine primary astrocytes and neurons
Article first published online: 18 JUL 2003
Journal of Neurochemistry
Volume 86, Issue 4, pages 907–916, August 2003
How to Cite
Klotz, L., Sastre, M., Kreutz, A., Gavrilyuk, V., Klockgether, T., Feinstein, D. L. and Heneka, M. T. (2003), Noradrenaline induces expression of peroxisome proliferator activated receptor gamma (PPARγ) in murine primary astrocytes and neurons. Journal of Neurochemistry, 86: 907–916. doi: 10.1046/j.1471-4159.2003.01909.x
- Issue published online: 21 JUL 2003
- Article first published online: 18 JUL 2003
- Received October 21, 2002; revised manuscript received April 30, 2003; accepted May 2, 2003.
- Alzheimer disease;
- locus ceruleus;
Cerebral inflammatory events play an important part in the pathogenesis of Alzheimer's disease (AD). Agonists of the peroxisome proliferator-activated receptor gamma (PPARγ), 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 PPARγ-mediated suppression of inflammation we investigated the influence of NA on PPARγ expression in murine primary cortical astrocytes and neurons. Incubation of astrocytes and neurons with 100 µm NA resulted in an increase of PPARγ mRNA as well as PPARγ protein levels in both cell types. These effects were blocked by the β-adrenergic antagonist propranolol but not by the α-adrenergic antagonist phentolamine, suggesting that they might be mediated by β-adrenergic receptors. Our results indicate for the first time that PPARγ 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 PPARγ levels. Conversely, decreased NA due to LC cell death in AD may reduce endogenous PPARγ expression and therefore potentiate neuroinflammatory processes.