Key points The present study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with the effect lasting for ∼60–70 min. We directly measured tDCS‐induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme‐linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of GABA and glutamate in the stimulated cortical area. Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA‐ and glutamate‐synthesizing enzymes, respectively. Abstract Transcranial direct current stimulation (tDCS) evokes long‐lasting neuronal excitability in the target brain region. The underlying neural mechanisms remain poorly understood. The present study examined tDCS‐induced alterations in neuronal activities, as well as the concentration and synthesis of GABA and glutamate (GLU), in area 21a (A21a) of cat visual cortex. Our analysis showed that anodal and cathodal tDCS respectively enhanced and suppressed neuronal activities in A21a, as indicated by a significantly increased and decreased amplitude of visually evoked field potentials (VEPs). The tDCS‐induced effect lasted for ∼60–70 min. By contrast, sham tDCS had no significant impact on the VEPs in A21a. On the other hand, the concentration of GABA, but not that of GLU, in A21a significantly decreased after anodal tDCS relative to sham tDCS, whereas the concentration of GLU, but not that of GABA, in A21a significantly decreased after cathodal tDCS relative to sham tDCS. Furthermore, the expression of GABA‐synthesizing enzymes GAD65 and GAD67 in A21a significantly decreased in terms of both mRNA and protein concentrations after anodal tDCS relative to sham tDCS, whereas that of GLU‐synthesizing enzyme glutaminase (GLS) did not change significantly after anodal tDCS. By contrast, both mRNA and protein concentrations of GLS in A21a significantly decreased after cathodal tDCS relative to sham tDCS, whereas those of GAD65/GAD67 showed no significant change after cathodal tDCS. Taken together, these results indicate that anodal and cathodal tDCS may selectively reduce GABA and GLU syntheses and thus respectively enhance and suppress neuronal excitability in the stimulated brain area.

BackgroundFungi colonize the human gut and might play a key role in the pathogenesis of ulcerative colitis (UC). However, studies on the fungal composition in the gut (especially adhering to the intestinal mucosa) of UC patients is limited.ResultsThe number of fungi decreased significantly in inflamed mucosa compared with that in HS mucosa. Fifteen major genera were examined, among which Wickerhamomyces, unidentified genus of Saccharomycetales, Aspergillus, Sterigmatomyces, and Candida showed increasing trends, whereas Exophiala, Alternaria, Emericella, Epicoccum, Acremonium, Trametes, and Penicillium showed decreasing trends in UC patients compared to the HS. The pro-inflammatory cytokines (IL-Iβ, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) were up-regulated in the UC group. The genera Wickerhamomyces, Nigrospora, and Penicillium were positively correlated, while Sporobolomyces and Trametes were negatively correlated with the expression of several colonic pro-inflammatory cytokines and the Baron and/or Mayo score.ConclusionsOur study confirms the alteration of the colonic fungal microbiota in the UC patients, which might be associated with mucosal inflammation and pathogenesis of UC. Further studies need to identify the roles of different intestinal fungi in detail, and to determine the mechanism of the host-fungal interaction underlying the development of UC.MethodsMucosal samples of inflamed descending colon from 14 active UC patients and 15 healthy subjects (HS) were analyzed by high-throughput sequencing to compare the fungal microbiota. The expressions of pro-inflammatory cytokines (IL-Iβ, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) in intestinal mucosal tissues were examined. The Baron and Mayo scores of UC patients were evaluated, and the correlation between intestinal fungal composition and intestinal inflammatory status was analyzed.

AIMTo analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease (IBD).METHODSFecal samples from 15 patients with Crohn’s disease (CD) (11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis (UC) and 13 healthy individuals were collected and subjected to 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified from all samples and sequenced by the Illumina MiSeq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software.RESULTSCommunity richness (chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC (in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores.CONCLUSIONOur study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.

Cognitive impairment is one of the most common and devastating neuropsychiatric sequelae after traumatic brain injury (TBI), and hippocampal neuronal survival plays a causal role in this pathological process. Resolvin D1 (RvD1), an important endogenous specialized pro‐resolving mediator, has recently been reported to exert a potent protective effect on mitochondria. This suggests that RvD1 may suppress neuroinflammation and protect astrocytic mitochondria at the same time to play further neuroprotective roles. C57BL/6 mice subjected to TBI using a controlled cortical impact device were used for in vivo experiments. Cultured primary mouse astrocytes and an N2a mouse neuroblastoma cell line were used for in vitro experiments. In TBI mice, RvD1 significantly ameliorated cognitive impairment, suppressed gliosis and alleviated neuronal loss in the hippocampus. To explore the mechanism underlying this activity, we verified that RvD1 can induce a higher level of mitophagy to remove damaged mitochondria and eliminate extra mitochondria‐derived reactive oxygen species (mitoROS) by activating ALX4/FPR2 receptors in astrocytes. In an in vitro model, we further confirmed that RvD1 can protect mitochondrial morphology and membrane potential in astrocytes and thereby enhance the survival of neurons. Meanwhile, RvD1 was also shown to increase the expression of brain‐derived neurotrophic factor and glutamate aspartate transporter in the hippocampus following TBI, which indicates a possible way by which RvD1 increases the supportive function of astrocytes. These findings suggest that RvD1 may be a potent therapeutic option for ameliorating cognitive impairment following TBI by controlling neuroinflammation and protecting astrocytic mitochondria. image