Mineralocorticoid receptor expression and increased survival following neuronal injury.
Glucocorticoids, acting via the mineralocorticoid receptor, are required for granule neuronal survival in the rat dentate gyrus. Whether this mineralocorticoid receptor-mediated neuroprotective effect has more general applicability is unknown. Here we report increased mineralocorticoid receptor expression in rat hippocampal and cortical neurons exposed in vitro to low levels of staurosporine and in rat hippocampal pyramidal neurons exposed in vivo to hypothermic transient global ischaemia. In both the cell culture system and the in vivo system increased mineralocorticoid receptor expression is associated with increased neuronal survival, and this increase is reversed by mineralocorticoid receptor antagonism. Modulation of mineralocorticoid receptor gene expression may therefore be an important target for reduction of brain injury in conditions caused by cerebral ischaemia including brain damage following cardiac arrest and stroke.
Macleod
Malcolm R
MR
Endocrinology Unit, Molecular Medicine Centre, Edinburgh University, Scotland. malcolm@apoptosis.freeserve.co.uk
Johansson
Inga-Maj
IM
Söderström
Ingegerd
I
Lai
Maggie
M
Gidö
Gunilla
G
Wieloch
Tadeusz
T
Seckl
Jonathan R
JR
Olsson
Tommy
T
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001930:Brain Injuries / Q000503:physiopathology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007035:Hypothermia / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007511:Ischemia / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D019311:Staurosporine