Plos One
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Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. ⋯ Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress.
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Tetrodotoxin-resistant (TTX-R) sodium channels Na(V)1.8 and Na(V)1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported Na(V)1.8, roles of Na(V)1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting Na(V)1.8 and Na(V)1.9 on inflammatory pain. ⋯ Intrathecal (i.t.) delivery of AS ODN was used to down-regulate Na(V)1.8 or Na(V)1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only Na(V)1.8 AS ODN, but not Na(V)1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels Na(V)1.8 and Na(V)1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain.
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Interstitial fibrosis plays an important role in progressive renal dysfunction in autosomal dominant polycystic kidney disease (ADPKD). In our previous studies, we confirmed that PPAR-γ agonist, rosiglitazone could protect renal function and prolong the survival of a slowly progressive ADPKD animal model by reducing renal fibrosis. However, the mechanism remains unknown. ⋯ ADPKD cyst-lining epithelial cells participate in TGF-β1 mediated fibrogenesis. Rosiglitazone could suppress TGF-β1-induced collagen type I and fibronectin expression in ADPKD cyst-lining epithelia through modulation of the Smad2 pathway. Our study may provide therapeutic basis for clinical applications of rosiglitazone in retarding the progression of ADPKD.
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Emotion and reward have been proposed to be closely linked to conscious experience, but empirical data are lacking. The anterior cingulate cortex (ACC) plays a central role in the hedonic dimension of conscious experience; thus potentially a key region in interactions between emotion and consciousness. Here we tested the impact of emotion on conscious experience, and directly investigated the role of the ACC. ⋯ Mirroring behavioural findings, we found significant differences in the LFPs after around 500 ms (lasting 30 ms) in conscious trials between happy and sad faces, while no effect was found in subliminal trials. We thus demonstrate a striking impact of emotion on conscious experience, with positive emotional stimuli enhancing conscious reportability. In line with previous studies, the data indicate a key role of the ACC, but goes beyond earlier work by providing the first direct evidence of interaction between emotion and conscious experience in the human ACC.
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Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. ⋯ CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.