title: The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids.
abstract: Previous studies have shown that strength exercise improves memory and increases expression of a myriad of proteins involved on neuronal survival and synaptic plasticity in the hippocampus. Conversely, chronic exposure to supraphysiological levels of anabolic androgenic steroids (AAS) can induce psychiatric abnormalities, cognitive deficits, impair neurotransmission, alter the levels of neurotrophic factors, decrease cell proliferation and neurogenesis, and enhance neuronal cell death. In the present study, we investigated the effects of the AAS nandrolone decanoate (ND) administration during a strength exercise program on cell proliferation, apoptotic status and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Adult male Wistar rats were subjected to 4 weeks of progressive strength exercise in a vertical ladder apparatus with or without daily doses (5.0 mg/kg, SC) of ND. Immunohistochemistry analysis revealed that strength exercise increased significantly the number of Ki-67-positive cells (a cell proliferation marker) in dentate gyrus (DG) of hippocampus. However, this effect was abrogated when strength exercise was combined with ND. Although western blot analysis of whole hippocampus showed no significant differences in Bax and Bcl-2 protein expression among groups, the immunoreactivity of the pro-apoptotic protein Bax was significantly increased in DG, CA1 and CA3 hippocampal subfields of sedentary rats treated with ND. Moreover, the increase in the immunoreactivity of anti-apoptotic protein Bcl-2 (DG and CA3) induced by strength exercise was diminished by ND. There were no significant differences in BDNF expression among experimental groups. Therefore, the present findings suggest that the beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling are impaired by ND.
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil; Department of Exercise Physiology, Faculdade de Minas (FAMINAS), Muriaé-Minas Gerais, 36880-000, Brazil.
authors.forename: Fabiano Guimarães
authors.initials: FG
authors.lastname: Novaes Gomes
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil.
authors.forename: Jansen
authors.initials: J
authors.lastname: Fernandes
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Vannucci Campos
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-900, Brazil.
authors.forename: Ricardo Cardoso
authors.initials: RC
authors.lastname: Cassilhas
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-900, Brazil.
authors.forename: Gustavo Monteiro
authors.initials: GM
authors.lastname: Viana
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-900, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil.
authors.forename: Marta Karavisch
authors.initials: MK
authors.lastname: de Moraes Rêgo
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil.
authors.forename: Pedro Ivo
authors.initials: PI
authors.lastname: Buainain
authors.affiliation: Department of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-900, Brazil.
authors.forename: Esper Abrão
authors.initials: EA
authors.lastname: Cavalheiro
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil. Electronic address: arida.nexp@epm.br.
authors.forename: Ricardo Mario
authors.initials: RM
authors.lastname: Arida
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D010805:Physical Conditioning, Animal / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055070:Resistance Training; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D045930:Anabolic Agents; D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009277:Nandrolone; D000077603:Nandrolone Decanoate
keywords: Anabolic androgenic steroids; Apoptosis; BDNF; Hippocampus; Neuroplasticity; Strength exercise