title: Calcitonin potentiates oxygen-glucose deprivation-induced neuronal death.
abstract: Calcitonin is a hormone that decreases plasma calcium through inhibition of osteolysis. It is used in the treatment of osteoporosis and other bone disorders. 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 neurons, and salmon calcitonin has been shown to alter neuronal activity. Since 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 deprivation, staurosporine, oxygen-glucose deprivation, kainate, and NMDA were tested. Salmon calcitonin had no effect on apoptotic cell death in cortical cultures. However, acute treatment with salmon calcitonin (1-1000 nM) caused significant potentiation of neuronal death induced by oxygen-glucose deprivation. Similarly, salmon calcitonin potentiated cell death induced by exposure to kainate. In contrast, it did not potentiate cell death induced by exposure to NMDA. In fact, addition of a high concentration (1000 nM) of salmon calcitonin attenuated NMDA toxicity. These results indicate that calcitonin is not a survival factor for cortical neurons; however, it can alter excitotoxic cell death. The most interesting, and disturbing, effect is the ability of low concentrations of salmon calcitonin to potentiate oxygen-glucose deprivation-induced cell death.
authors.affiliation: Department of Biomedical Sciences, Marquette University, 561 N. 15th Street, Room 426, Milwaukee, Wisconsin 53233, USA.
authors.forename: M
authors.initials: M
authors.lastname: Asrari
authors.forename: D
authors.initials: D
authors.lastname: Lobner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012474:Salmon; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D016202:N-Methylaspartate; D002116:Calcitonin; D019311:Staurosporine; D005947:Glucose; D010100:Oxygen; D007608:Kainic Acid