Effects of aging and glucocorticoid treatment on monoamine oxidase subtypes in rat cerebral cortex: therapeutic implications.
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is more common in elderly depression than in younger cohorts, resulting in elevated glucocorticoid levels. Effectiveness of antidepressant drugs is also impaired in these patients. We evaluated the effects of continuous infusions of dexamethasone on monoamine oxidase (MAO) subtypes in aged rat brain to determine whether unique interactions of glucocorticoids and aging could contribute to abnormal transmitter disposition. Aged rats given dexamethasone showed robust induction of both MAO A (threefold increase) and B (30% increase) in the frontal/parietal cortex, effects in the opposite direction from those seen in young rats treated with glucocorticoids. Our results support the view that depression in the elderly may have biologically discrete components that make it differ from depression in younger people. These distinctions may influence the etiology and therapy of depression, while at the same time providing potential biomarkers (such as platelet MAO) that may serve to predict successful treatment outcome in patient subpopulations.
Slotkin
T A
TA
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
Seidler
F J
FJ
Ritchie
J C
JC
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D003907:Dexamethasone / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D003907:Dexamethasone; D008995:Monoamine Oxidase