Regulation of the nicotinic receptor alpha7 subunit by chronic stress and corticosteroids.
The alpha7 subunit of the nicotinic acetylcholine receptor (NAchRalpha7) is one of the principal brain receptors for nicotine and is thought to be a mediator of nicotine's pro-cognitive effects. While nicotine is known to interact with the stress axis, little is known about the effect of stress or corticosteroids on the expression in the hippocampus, a brain region important to both cognition and stress reactivity. We examined the effects of chronic (21 day) restraint stress (CRS) and adrenalectomy with hormone replacement with the selective mineralocorticoid receptor (MR) agonist aldosterone, the selective glucocorticoid receptor (GR) agonist RU28,362 or corticosterone for 7 days, on the hippocampal expression of NAchRalpha7 mRNA and protein, as measured by (125)I alpha-Bungarotoxin autoradiography. We found that CRS increased the levels of NAchRalpha7 mRNA in the CA1, CA3 and dentate gyrus while levels of the protein were lowered by the same treatment. Corticosteroid replacement showed a GR specific increase in NAchRalpha7 mRNA, consistent with a corticosteroid mediated effect of CRS. While the mechanism behind these observations is as yet unclear, they may be neuroprotective against the damaging effects of CRS or an example of adaptation to the allostatic load produced by CRS.
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10065, USA. rhunter@rockefeller.edu
Richard G
RG
Hunter
Erik B
EB
Bloss
Katharine J
KJ
McCarthy
Bruce S
BS
McEwen
D000305:Adrenal Cortex Hormones / Q000378:metabolism* / Q000494:pharmacology; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003345:Corticosterone / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000305:Adrenal Cortex Hormones; D000732:Androstanols; C579165:Chrna7 protein, rat; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003345:Corticosterone