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

@entity20099 @entity308 @entity1249 @entity73 @entity2819 @entity1251 @entity460 @entity35
Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both @entity308 . 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 @entity73 . We implanted slow-release @entity2819 pellets into adrenally intact adult male @entity35 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 @entity35 with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in @entity1251 relative to sham-operated controls, but unchanged in dentate gyrus and @entity1249 . In contrast, the expression of the mRNA coding the alpha subunit of @entity460 -calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in @entity1251 . The expression of the mRNA coding the synaptic vesicle protein @entity20099 was unchanged in both @entity1251 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 @entity73 characteristic of aging and @entity308 .
