Rua Ramiro Barcelos
Rua Ramiro Barcelos
Muller A.P.,Rua Ramiro Barcelos |
Gnoatto J.,Rua Ramiro Barcelos |
Moreira J.D.,Rua Ramiro Barcelos |
Zimmer E.R.,Rua Ramiro Barcelos |
And 6 more authors.
Hippocampus | Year: 2011
Increasing evidence indicates that physical exercise induces adaptations at the cellular, molecular, and systemic levels that positively affect the brain. Insulin plays important functional roles within the brain that are mediated by insulin-receptor (IR) signaling. In the hippocampus, insulin improves synaptic plasticity, memory formation, and learning via direct modulation of GABAergic and glutamatergic receptors. Separately, physical exercise and central insulin administration exert relevant roles in cognitive function. We here use CF1 mice to investigate (i) the effects of voluntary exercise on hippocampal insulin signaling and memory performance and (ii) whether central insulin administration alters the effects of exercise on hippocampal insulin signaling and memory performance. Adult mice performed 30 days of voluntary exercise on running wheel and afterward both, sedentary and exercised groups, received intracerebroventricular (icv) injection of saline or insulin (0.5-5 mU). Memory performance was assessed using the inhibitory avoidance and water maze tasks. Hippocampal tissue was measured for [U- 14C] glucose oxidation and the immunocontent of insulin receptor/signaling (IR, pTyr, pAktser473). Additionally, the phosphorylation of the glutamate NMDA receptor NR2B subunit and the capacity of glutamate uptake were measured, and immunohistochemistry was used to determine glial reactivity. Exercise significantly increased insulin peripheral sensitivity, spatial learning, and hippocampal IR/pTyrIR/pAktser473 immunocontent. Glucose oxidation, glutamate uptake, and astrocyte number also increased relative to the sedentary group. In both memory tasks, 5 mU icv insulin produced amnesia but only in exercised animals. This amnesia was associated a rapid (15 min) and persistent (24 h) increase in hippocampal pNR2B immunocontent that paralleled the increase in glial reactivity. In conclusion, physical exercise thus increased hippocampal insulin signaling and improved water maze performance. Overstimulation of insulin signaling in exercised animals, however, via icv administration impaired behavioral performance. This effect was likely the result of aberrant phosphorylation of the NR2B subunit. © 2010 Wiley-Liss, Inc.
Siqueira I.R.,Federal University of Rio Grande do Sul |
Elsner V.R.,Programa de Pos Graduacao em Ciencias Biologicas Fisiologia |
Leite M.C.,Rua Ramiro Barcelos |
Vanzella C.,Federal University of Rio Grande do Sul |
And 8 more authors.
Neurochemistry International | Year: 2011
Ascorbate, an intracellular antioxidant, has been considered critical for neuronal protection against oxidant stress, which is supported especially by in vitro studies. Besides, it has been demonstrated an age-related decrease in brain ascorbate levels. The aims of the present study were to investigate ascorbate uptake in hippocampal slices from old Wistar rats, as well as its neuroprotective effects in in vitro and in vivo assays. Hippocampal slices from male Wistar rats aged 4, 11 and 24 months were incubated with radiolabeled ascorbate and incorporated radioactivity was measured. Hippocampal slices from rats were incubated with different concentrations of ascorbate and submitted to H2O2-induced injury, cellular damage and S100B protein levels were evaluated. The effect of chronic administration of ascorbate on cellular oxidative state and astrocyte biochemical parameters in the hippocampus from 18-months-old Wistar rats was also studied. The ascorbate uptake was decreased in hippocampal slices from old-aged rats, while supplementation with ascorbate (2 weeks) did not modify any tested oxidative status in the hippocampus and the incubation was unable to protect hippocampal slices submitted to oxidative damage (H2O2) from old rats. Our data suggest that the decline of ascorbate uptake might be involved in the brain greater susceptibility to oxidative damage with advancing age and both in vitro and vivo assays suggest that ascorbate supplementation did not protect hippocampal cells. © 2011 Elsevier Ltd. All rights reserved.