In vitro gender differences in neuronal survival on hypoxia and in 17|[beta]|-estradiol-mediated neuroprotection

doi:doi:10.1038/sj.jcbfm.9600056

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Journal of Cerebral Blood Flow & Metabolism (2005) 25, 427–430. doi:10.1038/sj.jcbfm.9600056 Published online 2 February 2005

In vitro gender differences in neuronal survival on hypoxia and in 17-estradiol-mediated neuroprotection

The study has been supported by the DFG (CMPB).

Andrea Heyer^1,*, Martin Hasselblatt^1,*, Nicolas von Ahsen², Heinz Häfner³, Anna-Leena Sirén¹ and Hannelore Ehrenreich¹

¹Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
²Department of Clinical Chemistry, Georg-August University, Göttingen, Germany
³Central Institute of Mental Health, Mannheim, Germany

Correspondence: Dr H Ehrenreich, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, D-37075 Göttingen, Germany. E-mail: ehrenreich@em.mpg.de

^*These authors contributed equally to this paper.

Received 23 August 2004; Revised 9 September 2004; Accepted 15 September 2004; Published online 2 February 2005.

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Abstract

Gender differences in neuropsychiatric disease are recognized but not well understood. Investigating the survival of primary rat hippocampal neurons in culture, we found significant and inverted gender differences on normoxia versus hypoxia. Male cells were more resistant under normoxia but more vulnerable under hypoxia than female cells. Male vulnerability pattern was acquired in cells from neonatally testosterone-primed females. Estrogens, acting via membrane receptors, had a higher neuroprotective power in male neurons, explained at least in part by the pronounced increase in estrogen receptor beta/alpha ratio during hypoxia in male cells only.