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Butyrate inhibits visceral allodynia and colonic hyperpermeability in rat models of irritable bowel syndrome
Get PDFLipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral allodynia and gut hyperpermeability via corticotropin-releasing factor (CRF) and proinflammatory cytokines, which is a rat irritable bowel syndrome (IBS) model. As butyrate is known to suppress the release of proinflammatory cytokine, we hypothesized that butyrate alleviates these colonic changes in IBS models. The visceral pain was assessed by electrophysiologically measuring the threshold of abdominal muscle contractions in response to colonic distention. Colonic permeability was determined by measuring the absorbance of Evans blue in colonic tissue. Colonic instillation of sodium butyrate (SB; 0.37-2.9 mg/kg) for 3 days inhibited LPS (1 mg/kg)-induced visceral allodynia and colonic hyperpermeability dose-dependently. Additionally, the visceral changes induced by repeated WAS (1 h for 3 days) or CRF (50 µg/kg) were also blocked by SB. These effects of SB in the LPS model were eliminated by compound C, an AMPK inhibitor, or GW9662, a PPAR-γ antagonist, NG-nitro-L-arginine methyl ester, a NO synthesis inhibitor, naloxone or sulpiride. SB attenuated visceral allodynia and colonic hyperpermeability in animal IBS models. These actions may be AMPK and PPAR-γ dependent and also mediated by the NO, opioid and central dopamine D2 pathways. Butyrate may be effective for the treatment of IBS
抑肝散はミクログリアに抗炎症作用を示し、脳梁におけるクプリゾン誘発性脱髄を抑制する
Get PDFMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown. In this study, female C57BL/6 mice were fed a diet containing 0.2% cuprizone (bis-cyclohexanone oxaldihydrazone) to induce demyelination in the corpus callosum. We investigated whether or not yokukansan reduces cuprizone-induced demyelination using immunohistochemical analyses. Furthermore, we examined the in vitro anti-inflammatory effects of yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Luxol fast blue staining and immunostaining for myelin basic protein demonstrated that yokukansan reduces demyelination of the corpora callosa of cuprizone-fed mice. In addition, yokukansan significantly decreased the number of activated microglial cells in the corpora callosa of cuprizone-fed mice. Furthermore, treatment with 500 μg/ml yokukansan suppressed the expression of interleukin-1β and inducible nitric-oxide synthase mRNA and protein in LPS-stimulated BV2 cells. These findings suggest that yokukansan reduces demyelination owing to anti-inflammatory effects on microglia. As yokukansan has few adverse effects, yokukansan has the potential to be a novel option to treat MS.博士（医学）旭川医科大
Premotor Cortex Provides a Substrate for the Temporal Transformation of Information During the Planning of Gait Modifications.
Get PDFThis is a pre-copyedited, author-produced version of an article accepted for publication in [Cerebral Cortex] following peer review. The version of record [Author’s Original Version] is available online at:https://doi.org/10.1093/cercor/bhz039We tested the hypothesis that the premotor cortex (PMC) in the cat contributes to the planning and execution of visually guided gait modifications. We analyzed single unit activity from 136 cells localized within layer V of cytoarchitectonic areas 6iffu and that part of 4δ within the ventral bank of the cruciate sulcus while cats walked on a treadmill and stepped over an obstacle that advanced toward them. We found a rich variety of discharge patterns, ranging from limb-independent cells that discharged several steps in front of the obstacle to step-related cells that discharged either during steps over the obstacle or in the steps leading up to that step. We propose that this population of task-related cells within this region of the PMC contributes to the temporal evolution of a planning process that transforms global information of the presence of an obstacle into the precise spatio-temporal limb adjustment required to negotiate that obstacle