title: Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures.
abstract: Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 μM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 μM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone's effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-α expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-α remained high. The present study showed that in stress-like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro-apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-α may be connected with the adverse effects of corticosterone on brain cell viability.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kurek
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.|Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London, WC1E 6BT, UK.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kucharczyk
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Detka
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ślusarczyk
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Trojan
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Głombik
authors.affiliation: Department of Veterinary Science, Faculty of Animal Science, University of Agriculture, 24/28 Mickiewicza Street, 30-059, Kraków, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Bojarski
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ludwikowska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland. budzisz@if-pan.krakow.pl.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism* / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D020932:Nerve Growth Factor; C505410:Casp3 protein, rat; D053148:Caspase 3; D003345:Corticosterone
keywords: Apoptosis; Corticosterone; Glutamate; Hippocampus; Organotypic cultures