Cognitive protection by
steroids
European Journal of Neuroscience ENJ Vol 18, no.1, 117-124
7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces
ischaemia-induced neuronal damage both in vivo and in vitro
Ashley K. Pringle, 1 Werner Schmidt, 2 Jackie K. Deans, 1
Ernst Wulfert, 3 Klaus G. Reymann 2,4 and Lars E. Sundstrom 1
1 Clinical Neurosciences,
Centre for Neurosciences, University of
Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16
7PX, UK 2 Research Institute Applied
Neurosciences, Magdeburg, Germany 3 Hunter-Fleming Ltd,
Regus House, Temple Quay, Bristol BS1 6EA, UK
4 Leibniz Institute for
Neurobiology, Magdeburg, Germany
Correspondence: Dr Ashley Pringle, as
above.
E-mail: akp1@soton.ac.uk
Recent evidence suggests that
steroids such as oestradiol reduce ischaemia-induced neurodegeneration in both in vitro and in vivo models [lack of
oxygen-blood causing reduced functions].
A cytochrome P450 enzyme termed cyp7b that 7-hydroxylates many steroids
is expressed at high levels in brain, although the role of 7-hydroxylated
steroids is unknown. We have tested the hypothesis that the steroid-mediated
neuroprotection is dependent on the formation of 7-hydroxy metabolites.
Organotypic hippocampal slice cultures were prepared from Wistar rat pups and
maintained in vitro for 14 days. Cultures were then
exposed to 3 h hypoxia [lack of oxygen as during a stroke] and neuronal
damage assessed 24 h later using propidium iodide fluorescence as a marker
of cell damage. Neurodegeneration
occurred primarily in the CA1 pyramidal cell layer. The steroids oestradiol,
dehydroepiandrosterone and epiandrosterone (EPIA) were devoid of
neuroprotective efficacy when present at 100 nm
pre-, during and post-hypoxia. The 7-hydroxy metabolites of EPIA, 7α-OH-EPIA
and 7β-OH-EPIA significantly reduced neurotoxicity at
100 nm and 10 nm. 7β-OH-EPIA was also neuroprotective in two in
vivo rat models of
cerebral ischaemia: 0.1 mg/kg 7β-OH-EPIA significantly reduced hippocampal
cell loss in a model of global forebrain ischaemia, whereas 0.03 mg/kg was
neuroprotective in a model of focal ischaemia even when administration was
delayed until 6 h after the onset of ischaemia. Taken together, these data demonstrate
that 7-hydroxylation of steroids
confers neuroprotective efficacy, and that 7β-OH-epiandrosterone represents a
novel class of neuroprotective compounds with potential for use in acute
neurodegenerative diseases.
Received 24 April 2003, accepted 30 April 2003
Another study (double blind) found that 7-keto DHEA
in an organic
preparation with a cocktail of herbs in an 8 week period produced significant
weight loss (mean ± SD loss, 2.15 ± 2.38 kg, but only 0.72 ± 2.12 kg for
placebo group) .
At http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VS8-467SPMX-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=10&md5=10235d4c9984971a7fd29b7a4e2e4672
Published by Elsevier Science, accepted February
2002.
