Neuroscience
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Exercise and antidepressants used independently have been shown to increase hippocampal brain-derived neurotrophic factor (BDNF) and neurogenesis. Despite the fact that patients with depression are often prescribed both, the effects of the exercise and fluoxetine antidepressant treatment used in combination are unknown. Using C57Bl/10 female mice, BDNF protein, insulin-like growth factor 1 (IGF-1) protein and neurogenesis were measured in the hippocampus after 21 days of wheel running, 21 days of fluoxetine antidepressant therapy (daily i.p. injections of 5 mg/kg, 10 mg/kg or 25 mg/kg) and the combination of the two. ⋯ Furthermore, spinal cord cytogenesis decreased with fluoxetine treatment. The combined wheel running and fluoxetine groups did not show synergistic results. Thus, the hippocampus and the spinal cord respond in distinct ways to wheel running and fluoxetine, and a prior induction of BDNF, IGF-1 or cytogenesis is unlikely to be the mechanism for wheel running providing a margin of protection against SCI.
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Nerve cell injury by unconjugated bilirubin (UCB) has been implicated in brain damage during neonatal hyperbilirubinemia, particularly in the preterm newborn. Recently, it was shown that UCB is a substrate for the multidrug resistance-associated protein 1 (Mrp1), an ATP-dependent efflux pump, which may decrease UCB intracellular levels. To obtain a further insight into the role of Mrp1 in the increased vulnerability of immature cells to UCB, we evaluated the mRNA and the protein levels of Mrp1 throughout differentiation in primary cultures of rat neurons and astrocytes. ⋯ The results are the first to demonstrate that Mrp1 is expressed in neurons and that both mRNA and protein levels of Mrp1 increase with cell differentiation. Additionally, inhibition of Mrp1 was associated with an increase in UCB toxic effects, namely cell death, cell dysfunction, and secretion of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, as well as of glutamate. These results point to a novel role of Mrp1 in the susceptibility of premature babies to UCB encephalopathy, and provide a startup point for the development of a new therapeutic strategy.