Impairment of long-term potentiation in the CA1, but not dentate gyrus, of the hippocampus in Obese Zucker rats

Obese Zucker rat (OZR) is a genetic model of obesity with noninsulin-dependent diabetes and hypertension. The OZR exhibit hyperinsulinemia, hyperlipidmia, and high circulating glucocorticoid levels. We have shown previously that long-term potentiation (LTP) is impaired in the CA1 region of the hippocampus of OZR. In the present work, although electrophysiological recording from anesthetized OZR hippocampus showed impaired UP in the CA1, an intact UP was recorded in the dentate gyrus (DG) region of the hippocampus of the same OZR. Thus, UP is differentially impaired in the CA1 compared with the DG region of OZR hippocampus. Immunoblotting was used to investigate the molecular mechanism responsible for impairment of UP in the CA1 but not in the DG region. Analysis revealed reduction in the levels of phosphorylated calcium-dependent calmodulin kinase 11 (P-CaMKII) and total CaMKII in the CA1 region of OZR. However, in the DG region, reduction was observed only in the levels of total CaMKII, with no change in P-CaMKII levels. The ratio of P-CaMKII to total CaMKII was increased in the DG but not in the CA1 area of hippocampus of OZR. Although unchanged in the CA1, calcineurin levels were significantly reduced in the DG of OZR. These findings suggest that the DG might possess a compensatory mechanism whereby calcineurin levels are reduced to allow sufficient P-CaN4KII to produce an apparently normal UP in the DG area of OZR hippocampus.