Long-term effects of corticosterone on behavior, oxidative and energy metabolism of parietotemporal cerebral cortex and hippocampus of rats: comparison to intracerebroventricular streptozotocin

Abstract

We studied the effect of long-term application of corticosterone (CORT) s.c. the equivalent of cortisol in rats, on behavior, oxidative and energy metabolism in brain parietotemporal cortex and hippocampus of 1-year-old male Wistar rats. The data were compared with results derived from long-term and low dose intracerebroventricular application of the diabetogenic drug streptozotocin (STZ) known to inhibit the function of the neuronal insulin receptor and generating an insulin resistant brain state. CORT reduced both working and reference memory increasingly with time and running parallel to the STZ-induced deficit. The effect of CORT on the activities of the glycolytic enzymes hexokinase, phosphofructokinase, pyruvate kinase, glyceraldehyde-3-phosphodehydrogenase, lactate dehydrogenase and, in tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase equaled in both experimental conditions and in both regions studied: significant decreases of all enzyme activities except lactate dehydrogenase which increased between three and fourfold of normal. The CORT- and STZ-induced marked fall in ATP was in the same range in the regions studied. Differences became obvious in the concentration of creatine phosphate in parietotemporal cerebral cortex showing no decrease after CORT obviously due to a different susceptibility of the CORT-receptor. It is discussed that both CORT and STZ may act on the neuronal insulin receptor in a similar way. However, further studies are needed on the gene expression of insulin and the insulin receptor and its protein levels to clarify the exact action of CORT on the neuronal insulin receptor function.