Role of phosphorylated CaMKII and calcineurin in the differential effect of hypothyroidism on LTP of CA1 and dentate gyrus.

Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus (DG) of hippocampus of anesthetized adult rats. Protein levels and activities of signaling molecules in both the CA1 and DG of surgically thyroidectomized and sham-operated euthyroid rats were measured. Basal levels of total calmodulin kinase II (CaMKII) protein in both the CA1 and DG were decreased in hypothyroidism. Marked reduction of basal P-CaMKII levels and CaMKII activity was seen in CA1, but not in the DG of the same hypothyroid animals. Basal levels of calmodulin and protein kinase Cgamma (PKCgamma) were decreased in CA1 but remained unchanged in the DG of hypothyroid rats. Basal calcineurin levels and activity, although enhanced in CA1, were reduced in the DG of hypothyroid rats. These findings suggest that the DG may possess a compensatory mechanism whereby calcineurin levels are reduced, to allow sufficient CaMKII activity to produce an apparently normal LTP in hypothyroid rats. (c) 2005 Wiley-Liss, Inc.