Neuroscience
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Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. ⋯ Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase (p=0.030) but no difference during the Pre-inflation phase (p=0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations.
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The glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/Siah1 signaling pathway has been recognized as a sensor of nitric oxide (NO). It is associated with a variety of injurious conditions, suggesting its therapeutic potential for spinal cord injury (SCI). Sivelestat sodium (SIV), a neutrophil elastase (NE) inhibitor initially used to treat acute lung injury, has been known to protect against compression-induced and ischemic SCI. ⋯ We also found that SIV suppressed apoptosis, NE and inducible nitric oxide synthase (iNOS) protein expressions, the number of NE and iNOS immunostained cells, the production of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), and the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) signaling in the spinal cord. The behavioral tests showed that SIV promoted functional recovery after traumatic SCI as reflected in the sustained increase in the Basso-Beattie-Bresnahan (BBB) scores throughout the observation period. In conclusion, our results reveal GAPDH/Siah1 as a novel signaling pathway during the progression of SCI, which can be blocked by SIV.
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Comparative Study
Endogenous opioids regulate glucocorticoid-dependent stress coping strategies in mice.
Coping skills are essential in determining the outcomes of aversive life events. Our research was aimed to elucidate the molecular underpinnings of different coping styles in two inbred mouse strains, C57BL/6J and SWR/J. We compared the influence of a preceding stressor (0.5h of restraint) on behavioral and gene expression profiles between these two strains. ⋯ We found that treatment with a glucocorticoid receptor (GR) agonist (dexamethasone (DEX), 4mg/kg) impaired the consolidation of fear memory in the C57BL/6J mice and that this effect was reversed by OR blockade (naltrexone (NTX), 2mg/kg). In parallel, a glucocorticoid receptor antagonist (mifepristone (MIF), 20mg/kg) reversed the effect of morphine (20mg/kg) on conditioned fear in the C57BL/6J mice. Our results suggest that in mice, stress-coping strategies are determined by opioid-dependent mechanisms that modulate activity of the HPA axis.
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iTRAQ technology-based identification of human peripheral serum proteins associated with depression.
Clinical depression is one of the most common and debilitating psychiatric disorders and contributes to increased risks of disability and suicide. Differentially expressed serum proteins may serve as biomarkers for diagnosing depression. In this study, samples from depressed patients are aggregated into a pool (22×100μL serum was used) and samples from healthy volunteers are aggregated into the other pool (20×100μL serum was used). ⋯ Finally, four differentially expressed proteins were validated by enzyme-linked immuno sorbent assay (ELISA). Proteomic studies revealed that levels of c-reaction protein (CRP), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), serum amyloid A1 (SAA1) and angiopoietin-like 3 (ANGPTL3) were substantially increased in depressed patients compared with the healthy control group. Therefore, these differentially expressed proteins may represent potential markers for the clinical diagnosis of depression.
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In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. ⋯ Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations.