Estrogen mediates neuroprotection via estrogen receptor α, not β, in a neuronal in vitro model

Estrogen hormone action is essential for developmental and reproductive functions, but various basic and clinical studies suggest also a protective role against chronic and acute neurodegenerative diseases, as Alzheimer’s disease, and cerebrovascular stroke.

By focussing on estrogen receptor (ER) dependent neuroprotective activities we stably transfected a human neuroblastoma cell line with ERα, ERβ and ER α/β cDNA. Interestingly, besides morphological changes ERα transfectants showed a higher survival rate under different stress conditions which agree and support findings that protection against brain injury is mediated by ERα, not β. Via a large scale DNA-Microarray analysis we found that ERα modifed the expression levels of genes involved in calcium homeostasis and neuronal signalling (CaM kinases), stress response (Hsp70), inflammatory response (JAKs) and cell survival, e.g. a strong up regulation of Bcl–2, a proto-oncogene that promotes cell suvival and down regulation of Caspase 3, which act as executor caspase in apoptotic transformation of neurons.

Together these findings display for the first time an ER subtype-specific expression profile in human neuronal cells. Our in vitro model and the expression data can help to further elucidate estrogenic effects and functions in various brain areas.

Supported by EU NoE CASCADE (FOOD-CT–2004–506319)