Calcitonin potentiates oxygen-glucose deprivation-induced neuronal death

Calcitonin is a hormone that decreases plasma calcium through inhibition of osteolysis. It is used in the treatment of osteoporosis and other bone dis orders. Salmon calcitonin is typically utilized in individuals for whom use of estrogen is contraindicated, for example, women at high risk for breast cancer. In addition to actions on bone, calcitonin may have effects on the central nervous system. Receptors for calcitonin are present on central ne urons, and salmon calcitonin has been shown to alter neuronal activity. Sin ce salmon calcitonin is used clinically, and it can have actions on neurons , the present studies were designed to determine whether salmon calcitonin could alter death of cortical neurons. The effects of salmon calcitonin on neuronal death induced by exposure of murine cortical cultures to serum dep rivation, staurosporine, oxygen-glucose deprivation, kainate, and NMDA were tested. Salmon calcitonin had no effect on apoptotic cell death in cortica l cultures. However, acute treatment with salmon calcitonin (1-1000 nM) cau sed significant potentiation of neuronal death induced by oxygen-glucose de privation. Similarly, salmon calcitonin potentiated cell death induced by e xposure to kainate. In contrast, it did not potentiate cell death induced b y exposure to NMDA. In fact, addition of a high concentration (1000 nM) of salmon calcitonin attenuated NMDA toxicity, These results indicate that cal citonin is not a survival factor for cortical neurons; however, it can alte r excitotoxic cell death. The most interesting, and disturbing, effect is t he ability of low concentrations of salmon calcitonin to potentiate oxygen- glucose deprivation-induced cell death. (C) 2001 Academic Press.