title: Mineralocorticoid receptor expression and increased survival following neuronal injury.
abstract: 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.
authors.affiliation: Endocrinology Unit, Molecular Medicine Centre, Edinburgh University, Scotland. malcolm@apoptosis.freeserve.co.uk
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.forename: Inga-Maj
authors.initials: IM
authors.lastname: Johansson
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Söderström
authors.forename: Maggie
authors.initials: M
authors.lastname: Lai
authors.forename: Gunilla
authors.initials: G
authors.lastname: Gidö
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Wieloch
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D019311:Staurosporine