Sex-Dependent Changes in the Gene Expression of UPR-Associated Calcium-Binding Proteins in the STZ-Induced Model of Alzheimer's Disease.

Although the causes of Alzheimer's disease (AD) are still unknown, the unfolded protein response (UPR) is considered the basis for the pathogenesis of many degenerative diseases, including AD. The incidence of AD is slightly higher in the female population; however, biases continue to raise questions as to whether gender is a risk factor for the disease, as insulin resistance is. In this study, we used a sporadic model of Alzheimer's disease, induced by intracerebroventricularly-administered streptozotocin (STZ) in Wistar rats, to evaluate potential modulations in proteins involved in the UPR and the dependence of alterations on the sex of the animals. The rats were evaluated at two time points; 4 and 16 weeks post-STZ. At 16 weeks, cognitive deficit was observed in all rats treated with STZ, as well as an increase in glial fibrillary acid protein (GFAP), and a reduction in synaptophysin in the hippocampus. However, at 4 weeks, cognitive deficit was found only in males, in association with a reduction in synaptophysin. With regard to neurochemical changes in the AD model of STZ, we found sex-dependent differences in the gene expression of OASIS (an ATF-6-like UPR sensor in astrocytes), calpastatin (inhibitor protein of calpain 1/2), calpain-10, calcineurin, sorcin and CHOP. Taken together, results obtained herein contribute to the understanding of the pathogenesis of AD and indicate that the STZ-triggered UPR observed may be sex-dependent.