title: Streptozotocin causes neurotoxic effect in cultured cerebellar granule neurons.
abstract: Streptozotocin (STZ) is a glucosamine-nitrosourea compound used for experimental simulation of sporadic Alzheimer's disease at intracerebroventricular administration in vivo. The studies of STZ influence on neurons of central nervous system performed on the primary cultures are practically absent. We have shown the application of STZ (1-5mM) in primary culture for 48h induced strong dose-dependent death in cultured cerebellar granule neurons. This toxic effect was decreased by pyruvate, insulin partially. Using the indicator Fluo-4 AM for measurements of intracellular calcium ions and tetramethylrhodamine ethyl ester (TMRE) for detection of changes of mitochondrial membrane potential in live cells we have shown that 5 h-exposure to STZ induced intensive increase of Fluo-4 and decrease TMRE fluorescence in neurons. STZ exposure caused considerable ultrastructural alterations in granule neurons: chromatin clumping, swelling of the endoplasmic reticulum and mitochondria, and disruption of the mitochondrial cristae. Probably, STZ significantly impaired glucose metabolism and mitochondrial function that, in turn, resulted in mitochondrial membrane potential damage, excessive calcium overload and neuronal death.
authors.affiliation: Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia.
authors.forename: Elisaveta E
authors.initials: EE
authors.lastname: Genrikhs
authors.affiliation: Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia. Electronic address: estelmash@mail.ru.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Stelmashook
authors.affiliation: M. V. Lomonosov Moscow State University, N. A. Belozersky Research Institute of Physico-Chemical Biology, Leninskye gory, 1, b. 40, 119991 Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Golyshev
authors.affiliation: Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia.
authors.forename: Olga P
authors.initials: OP
authors.lastname: Aleksandrova
authors.affiliation: Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia; M. V. Lomonosov Moscow State University, N. A. Belozersky Research Institute of Physico-Chemical Biology, Leninskye gory, 1, b. 40, 119991 Moscow, Russia.
authors.forename: Nickolay K
authors.initials: NK
authors.lastname: Isaev
mesh_terms: D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000008:administration & dosage; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D013311:Streptozocin
keywords: Calcium; Cultured neurons; Insulin; Mitochondrial membrane potential; Streptozotocin