Regional differences in brain monoamine oxidase subtypes in an animal model of geriatric depression: effects of olfactory bulbectomy in young versus aged rats.
Geriatric depression is often associated dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and with poor responsiveness to antidepressants that work through inhibition of monoamine reuptake; accordingly, it has been suggested that MAO inhibitors may represent a therapeutic alternative in this group. In the current study, we evaluated expression of MAO subtypes in brain regions of young and aged rats subjected to olfactory bulbectomy (OBX), a procedure that reproduces many of the biochemical and functional changes associated with human depression. Activities of both MAO A and B were elevated in aged rats as compared to young rats in most regions, but not in the midbrain, and the OBX lesion failed to produce any change in this pattern. These results stand in contrast to the differential effects of glucocorticoids, which reduce brain MAO in young animals but induce activity in aged rats. Our results support the view that the aged brain possesses biochemical characteristics that distinguish its monoamine biochemistry from that of young brain, and that these distinctions may work in conjunction with HPA axis dysregulation to influence the etiology and therapy of geriatric depression. The use of appropriate animal models for depression and for disruption of HPA axis function can allow for the testing of potential human biomarkers (such as platelet MAO) that may serve to predict treatment outcome.
Slotkin
T A
TA
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
Seidler
F J
FJ
Ritchie
J C
JC
D000367:Age Factors; D000818:Animals; D002531:Cerebellum / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology*; D003863:Depression / Q000201:enzymology*; D004195:Disease Models, Animal; D005852:Geriatric Psychiatry; D006624:Hippocampus / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009830:Olfactory Bulb / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D008995:Monoamine Oxidase