Protein S100B and physical exercise

Protein S100B has been used as a peripheral biochemical marker of brain injury and/or activity. However, recent studies have demonstrated that this protein is also increased in serum after physical exercise, although the interpretation of this finding remains controversial. Although predominantly released by astrocytes in the central nervous system, extracerebral sources of protein S100B have been suggested to contribute to the increase in serum levels of this protein. However, in the case of exercises that have an impact on the brain such as boxing, elevated levels are clearly associated with brain damage. More recently, some studies have proposed that protein S100B might be released by activated adipocytes and by damaged muscle cells. If confirmed experimentally, protein S100B might be potentially useful in sports training. We are currently investigating the potential role of serum protein S100B as an indicator of muscle damage. Therefore, the objective of this review was to discuss the current knowledge about the relationship between physical exercise and serum protein S100B and its possible leakage from muscle cells injured by exercise

Insulin activates microglia and increases COX-2/IL-1 beta expression in young but not in aged hippocampus

Brain insulin resistance and neuroinflammation are known to increase with age. Insulin exerts metabolic roles on neurons and astrocytes, but its effects on microglia is unclear. In this study we investigated whether insulin affected microglia in the hippocampus of young and aged rats. We injected intracerebroventricular (i.c.v.) insulin (20 mU) or vehicle for five days and evaluated microglial inflammatory markers in the hippocampus of young (3 months) Wistar rats. Increased microglial activation (Iba-1+CD68+cells) and COX-2/IL-1β levels in the hippocampus were found. Since the aged brain is an experimental model for brain insulin resistance and chronic neuroinflammation we submitted aged rats (22 months) to i.c.v. insulin/vehicle administration and found no significant increase in Iba-1+CD68+ microglia or COX-2/IL-1β levels. To further investigate whether insulin triggered transient or persistent proinflammatory responses, young rats were evaluated eight-days after the last insulin injection. Microglia were persistently activated, and COX-2 levels remained elevated in the hippocampus, which paralleled increased spatial memory performance in the Morris Water Maze behavioral task. To determine if microglia were directly responsive to insulin, primary microglia were challenged with insulin and increased Akt Ser473 phosphorylation, a protein activated by the insulin receptor, was detected. These data suggest that microglia in the hippocampus integrate insulin signaling and neuroinflammatory responses and that this signal is disrupted during chronic inflammation. In our concept, the disruption between microglia activation by insulin signaling is a new pathological mechanism behind insulin resistance in the aging brain

Alterações do sistema insulina/igf-1 na doença de machado-joseph: novas perspectivas para poliglutaminopatias

Membrane acid extrusion by Na(+)/H(+) exchange (NHE1) and Na(+)-HCO3(-) co-transport (NBC) is essential for maintaining a low cytoplasmic [H(+)] (∼60 nm, equivalent to an intracellular pH (pHi) of 7.2). This protects myocardial function from the high chemical reactivity of H(+) ions, universal end-products of metabolism. We show here that, in rat ventricular myocytes, fluorescent antibodies map the NBC isoforms NBCe1 and NBCn1 to lateral sarcolemma, intercalated discs and transverse tubules (t-tubules), while NHE1 is absent from t-tubules. This unexpected difference matches functional measurements of pHi regulation (using AM-loaded SNARF-1, a pH fluorophore). Thus, myocyte detubulation (by transient exposure to 1.5 m formamide) reduces global acid extrusion on NBC by 40%, without affecting NHE1. Similarly, confocal pHi imaging reveals that NBC stimulation induces spatially uniform pHi recovery from acidosis, whereas NHE1 stimulation induces pHi non-uniformity during recovery (of ∼0.1 units, for 2-3 min), particularly at the ends of the cell where intercalated discs are commonly located, and where NHE1 immunostaining is prominent. Mathematical modelling shows that this induction of local pHi microdomains is favoured by low cytoplasmic H(+) mobility and long H(+) diffusion distances, particularly to surface NHE1 transporters mediating high membrane flux. Our results provide the first evidence for a spatial localisation of [H(+)]i regulation in ventricular myocytes, suggesting that, by guarding pHi, NHE1 preferentially protects gap junctional communication at intercalated discs, while NBC locally protects t-tubular excitation-contraction coupling