17β-estradiol does not protect cerebellar granule cells from excitotoxicity or apoptosis
Article first published online: 31 JAN 2007
Journal of Neurochemistry
Volume 102, Issue 2, pages 354–364, July 2007
How to Cite
Miñano, A., Cerbón, M. A., Xifró, X., Malagelada, C., Aguilera, J. and Rodríguez-Alvarez, J. (2007), 17β-estradiol does not protect cerebellar granule cells from excitotoxicity or apoptosis. Journal of Neurochemistry, 102: 354–364. doi: 10.1111/j.1471-4159.2007.04475.x
- Issue published online: 31 JAN 2007
- Article first published online: 31 JAN 2007
- Received August 8, 2006; revised manuscript received November 16 2006; accepted January 16 2007.
- neuronal death;
Mounting evidences have suggested that 17β-estradiol (E2) could have a neuroprotective action in the CNS. In the present study, we wanted to study whether this estrogen was able to protect cerebellar granule cells (CGCs) from apoptosis or excitotoxicity. Our results suggest that E2 has no anti-apoptotic effect in CGCs cultures. The lack of phosphoinositide 3-kinase/Akt pathway activation in CGCs cultures could be on the basis of the failure of estradiol to protect CGCs from potassium-deprivation and ceramide-mediated apoptosis. Moreover, E2 does not protect CGCs from glutamate-mediated death despite activating the extracellular signal regulated kinase kinase/extracellular signal regulated kinase pathway, which suggests that extracellular signal regulated kinase kinase/extracellular signal regulated kinase pathway activation is not sufficient to sustain an estrogen-mediated neuroprotective effect in CGCs cultures. By contrast, we found that the estrogen had a significant neuroprotective effect against hydrogen peroxide-mediated neuronal death. This effect was due to the antioxidant properties of the chemical structure of estradiol, as the biological inactive isomer 17α-estradiol was also able to reduce hydrogen peroxide-mediated neuronal death.