Physical Exercise Exacerbates Memory Deficits Induced by Intracerebroventricular STZ but Improves Insulin Regulation of H2O2 Production in Mice Synaptosomes
Affiliations: [a] Departamento de Bioquímica, ICBS, UFRGS, Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Rua Ramiro Barcelos, Porto Alegre, RS, Brasil | [b] Programa de Pós-Graduação em Saúde & Comportamento Centro de Ciências da Vida e da Saúde Universidade Católica de Pelotas, Rua Almirante Barroso, Pelotas, Rio Grande do Sul, Brasil | [c] Instituto de Bioquímica Médica, Programa de Biofísica e Bioquímica Celular e Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Laboratório de Bioenergética e Fisiologia Mitocondrial, Cidade Universitária, Rio de Janeiro, Brasil
Correspondence:
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Correspondence to: Alexandre Pastoris Muller, PhD, Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Tel.: +55 51 33085557; Fax: +55 51 33085544; E-mail: [email protected].
Note: [1] Both authors contributed equally to this work.
Abstract: Insulin brain resistant state is associated with cognitive deficits and Alzheimer's disease by mechanisms that may involve mitochondrial damage and oxidative stress. Conversely, physical exercise improves cognitive function and brain insulin signaling. The intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) in rodents is an established model of insulin-resistant brain state. This study evaluates the effects of physical exercise on memory performance of i.c.v., STZ-treated mice(1 and 3 mg/kg) and whether insulin (50 and 100 ng/ml) modulates mitochondrial H2O2 generation in synaptosomes. S100B levels and SOD and CAT activities were assessed as markers of brain damage caused by STZ. Sedentary and exercise vehicle-treated mice demonstrated similar performance in object recognition memory task. In the water maze test, exercise vehicle-treated mice showed improvement performance in the acquisition and retrieval phases. The administration of STZ (1 mg/kg) before thirty days of voluntary physical exercise protocol impaired recognition and spatial memory only in exercised mice, whereas STZ (3 mg/kg) impaired the performance of sedentary and exercise groups. Moreover, STZ (3 mg/kg) increased hippocampal S100B levels in both groups and SOD/CAT ratio in the sedentary animals. Insulin decreased synaptosomal H2O2 production in exercised compared to sedentary mice; however, both STZ doses abolished this effect. Normal brain insulin signaling is mechanistically involved in the improvement of cognitive function induced by exercise through the regulation of mitochondrial H2O2 production. However, a prior blockade of brain insulin signaling with STZ abolished the benefits of exercise on memory performance and mitochondrial H2O2 regulation.
