Stress enhances expression of calcium-binding proteins and NMDAR subunit genes in the rat hippocampus.

Backgrounds: Oxidative stress impairs the function of calcium-binding proteins and deregulates calcium signaling in living organisms. We have previously explored the overexpression of calcium-binding protein genes in a reactive oxygen and nitrogen species-induced in vitro cell model of stress that leads to apoptosis. However, in in vivo models, low levels of stress leads to depressive-like behavior. Here, we aimed to analyze gene expression of major calcium-binding proteins (calcineurin, calmodulin, calsyntenin, synaptotagmin, and calreticulin) and N-methyl-d-aspartic acid (NMDA) receptor subunits (glutamate receptor ionotropic [GluN] GluN1, GluN2A, and GluN2B) in the hippocampus of stress-induced rats. Methods: Six-week-old male Wistar rats were assigned to two stress induction groups and a control group without stress (n = 6). Stress was induced by using H2O2 (3% in water) or by immobilization (using a sticky mat) over a period of 30 days. Expression of calcium-binding protein genes in the hippocampus, antioxidant assays, structural alterations in hippocampal neurons, and depressive-like behavior were determined. Results: Expression of genes encoding calcium-binding proteins calcineurin, calsyntenin, synaptotagmin and NMDA receptor subunit GluN1 was enhanced in both chemical and physical stress-induced rats compared with control rats (4.25 ± 0.05 vs. 1.03 ± 0.02, p < 0.05, 2.05 ± 0.08 vs. 1.03 ± 0.02, p < 0.005; 2.2 ± 0.4 vs. 1.02 ± 0.03, p < 0.05, 1.98 ± 0.07 vs. 1.02 ± 0.03, p < 0.005; 1.4 ± 0.6 vs. 1.15 ± 0.09, p < 0.05, 1.39 ± 0.05 vs. 1.15 ± 0.09, p < 0.005), respectively. In stress-induced rats, neurons in the CA2 region of the hippocampus were fewer and appeared disorganized compared with control rats. Furthermore, stress-induced rats showed decreased mobility and lower sucrose preference in behavioral studies compared with control rats. Conclusion: Lower levels of reactive oxygen and nitrogen species (RONS) can also lead to stress in rats by affecting their calcium signaling, buffering capacity in the neurons leading to depressive symptoms.