Neuroscience
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Many human and animal studies have implicated inflammation as a mediator of oxidative stress and a possible contributor to hippocampal atrophy in the pathophysiology of major depressive disorder. We aimed to examine the effect of peripheral, systemic inflammation on oxidative stress and apoptosis in the hippocampi of male and female mice. We hypothesized that (1) lipopolysaccharide (LPS) would induce depressive-like behavior and hippocampal oxidative stress after 1 day in males, and (2) that a single LPS exposure would result in hippocampal apoptosis at 28 days. ⋯ Moreover, males given LPS showed increased apoptosis. Our work will provide insight into the underlying biology in males and females with MDD, and potentially underlying differences between the sexes. Also, our work will hopefully inform optimal clinical treatments that may indeed differ between the sexes.
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LIMK2 is involved in neuronal functions by regulating actin dynamics. Different isoforms of LIMK2 are described in databanks. LIMK2a and LIMK2b are the most characterized. ⋯ Our results also suggest an implication of LIMK2-1 in neurite outgrowth and neurons arborization which appears to be affected by the p. S668P variation. Therefore our results suggest that LIMK2-1 plays a role in the developing brain, and that a rare variation of this isoform is a susceptibility factor in ID.
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Prolonged occupational exposure to hand-held vibrating tools leads to pain and reductions in tactile sensitivity, grip strength and manual dexterity. The goal of the current study was to use a rat-tail vibration model to determine how vibration frequency influences factors related to nerve injury and dysfunction. Rats were exposed to restraint, or restraint plus tail vibration at 62.5 Hz or 250 Hz. ⋯ There was an increase in glutathione, but no changes in other measures of oxidative activity in the peripheral nerve. However, measures of oxidative stress were increased in the dorsal root ganglia (DRG). These changes in pro-inflammatory factors and markers of oxidative stress in the peripheral nerve and DRG were associated with inflammation, and reductions in myelin basic protein and post-synaptic density protein (PSD)-95 gene expression, suggesting that vibration-induced changes in sensory function may be the result of changes at the exposed nerve, the DRG and/or the spinal cord.
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Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary cultured NS/PCs and in those of the adult mouse brain. ⋯ Although pathological and functional damages in the hippocampus induced by the neurotoxin trimethyltin were not significantly different between wild-type and Nox4-/- mice, the post-injury reactive proliferation of NS/PCs and neurogenesis in the subgranular zone (SGZ) of the dentate gyrus were significantly impaired in Nox4-/- animals. Restoration from the trimethyltin-induced impairment in recognition and spatial working memory was also significantly attenuated in Nox4-/- mice. Collectively, our findings suggest that Nox4 participates in NS/PC proliferation and neurogenesis in the hippocampus following injury, thereby helping to restore memory function.
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We investigated the dose dependence of the role of nociceptors in opioid-induced side-effects, hyperalgesia and pain chronification, in the rat. Systemic morphine produced a dose-dependent biphasic change in mechanical nociceptive threshold. At lower doses (0.003-0.03 mg/kg, s.c.) morphine induced mechanical hyperalgesia, while higher doses (1-10 mg/kg, s.c.) induced analgesia. ⋯ Thus, the induction of hyperalgesia, but not priming, by low-dose morphine, is MOR-dependent. In contrast, induction of both hyperalgesia and priming by high-dose morphine is MOR-dependent. The receptor at which low-dose morphine acts to produce priming remains to be established.