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Flattening the glucocorticoid rhythm causes changes in hippocampal expression of messenger RNAs coding structural and functional proteins: implications for aging and depression

Lookup NU author(s): Dr Sasha Gartside, Mel LeitchORCiD, Professor Richard McQuade



Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Publication metadata

Author(s): Gartside SE, Leitch MM, McQuade R, Swarbrick DJ

Publication type: Article

Publication status: Published

Journal: Neuropsychopharmacology

Year: 2003

Volume: 28

Issue: 5

Pages: 821-829

Date deposited: 23/10/2009

ISSN (print): 0893-133X

ISSN (electronic): 1470-634X

Publisher: Nature Publishing Group


DOI: 10.1038/sj.npp.1300104

Notes: Gartside, Sarah E Leitch, Melville M McQuade, Richard Swarbrick, Daniel J Research Support, Non-U.S. Gov't United States Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Neuropsychopharmacology. 2003 May;28(5):821-9. Epub 2003 Mar 5.


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