The microbiota-gut-brain axis transmits bidirectional communication between the gut and the central nervous system and links the emotional and cognitive centers of the brain with peripheral gut functions. This communication occurs along the axis via local, paracrine, and endocrine mechanisms involving a variety of gut-derived peptide/amine produced by enteroendocrine cells. Neural networks, such as the enteric nervous system, and the central nervous system, including the autonomic nervous system, also transmit information through the microbiota-gut-brain axis. Recent advances in research have described the importance of the gut microbiota in influencing normal physiology and contributing to disease. We are only beginning to understand this bidirectional communication system. In this review, we summarize the available data supporting the existence of these interactions, highlighting data related to the contribution of enteroendocrine cells and the enteric nervous system as an interface between the gut microbiota and brain.
Taste-2 receptors (TAS2Rs), which belong to the G-protein coupled receptor (GPCR) family, are receptors for bitter taste perception. The aim of this study was to investigate whether zinc deficiency affects the expression of TAS2R genes. The promoter activity of the TAS2R7, TAS2R8, and TAS2R42 genes were determined in Ca9-22 oral squamous cell carcinoma cells cultured in the presence or absence of zinc. Luciferase reporter assays showed that zinc deprivation inhibited TAS2R8 promoter activity, but not the promoter activity of the other two genes. Treatment of the cells with N,N,N’,N’-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN), an intracellular chelator of Zn2+, in the presence of 10% fetal bovine serum reduced TAS2R8 promoter activity. Truncation/deletion mutants of TAS2R8 promoter-luciferase constructs showed that the region from nucleotide −1152 to nucleotide −925 was critical for intracellular zinc dependency and contained a CCCTC-binding factor (CTCF) binding motif. A chromatin immunoprecipitation (ChiP) assay showed that CTCF bound specifically to this region, a binding abrogated by zinc deficiency, suggesting that CTCF plays a critical role in zinc-dependent bitter taste perception through TAS2R8.
Diabetes mellitus induces skeletal muscle dysfunction, such as decreased metabolic activity and capillarization. This study aimed to investigate the effects of aerobic low intensity exercise training on metabolic oxidative capacity and capillarization in skeletal muscle of non-obese diabetic rats. Eleven to twenty-five week-old male non-obese Spontaneous Diabetic Torii (SDT) rats (n = 11) and age-matched healthy male Sprague-Dawley SD rats (n = 11) were randomly assigned to either exercise or sedentary groups. The exercise training was performed on a low-speed motorized treadmill (15 m min−1) for 60 min per session, 5 sessions per week for 14 weeks in exercised groups. Sedentary SDT rats resulted in hyperglycemia, reduction of metabolic oxidative enzyme, and low percentage of oxidative fibers in the skeletal muscles. The low-intensity exercise training inhibited the growth-related increase in glucose level, and increased the muscle oxidative enzyme in exercised SDT rats compared with sedentary SDT rats. In addition, the exercise program prevented capillary regression in the skeletal muscle of diabetic rats. These results suggest that low-intensity exercise training may be an effective treatment to counter the detrimental effects of type 2 diabetes mellitus on the oxidative capacity and the capillary network of skeletal muscles.
Xeroderma pigmentosum (XP) involves a defect in the initial step of nucleotide excision repair (NER) and consists of eight genetic complementation groups (groups A–G and a variant). XP group A (XPA) patients have a high incidence of UV-induced skin tumors, immature testicular development, and neurological symptoms. In an earlier study, we have shown that XP group A (Xpa) gene-knockout mice (Xpa−/− mice) were highly sensitive to UV-induced skin carcinogenesis with a defect in NER and were highly susceptibility to spontaneous tumorigenesis with impaired spermatogenesis. However, the pathology of impaired spermatogenesis in Xpa−/− mice is unknown. To unravel the underlying pathology, we made a concerted effort using the testis of 3-month-old Xpa−/− mice. We found many large vacuoles in the seminiferous tubules of 3-month old Xpa−/− mice, while there were no large vacuoles in that of Xpa+/+ mice. Immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, showed degenerating cells with intense signal of LC3 in the seminiferous tubules, and immunoblotting revealed induction of LC3-II in the 3-month-old Xpa−/− mice. The results of the present study suggest autophagy induction as the possible mechanism underlying the impaired spermatogenesis in Xpa−/− mice. Therefore, Xpa−/− mice could be a useful model for investigating aging and male infertility with low expression of XPA.
The vomeronasal organ (VNO) is an accessory olfactory device related to reproductive behavior. The soft tissue of the tubular organ is composed of sensory/non-sensory epithelia and a highly developed vasculature, which in the latter the dilation and contraction of blood vessels are thought to contribute to pumping in and out luminal fluid or air, like penile erectile tissue. The present histological observation of the murine VNO revealed a more complicated vasculature than previously evaluated ones with large differences along the rostro-caudal axis. An immunohistochemical study for vasoactive substances displayed extremely dense innervation by cholinergic nerves containing nitric oxide synthase and VIP/PHI in the thick smooth muscle layer surrounding venous sinuses at light and electron microscopic levels. Furthermore, the differential distribution of cholinergic nerves and adrenergic nerves may provide a novel insight into the pumping mechanism of VNO.
Administration of cisplatin and methotrexate significantly increased 5-hydroxytryptamine (5-HT) release from intestinal tissues isolated at 72 h after administration in rats. Daily administration with nafamostat mesilate, a potent serine protease inhibitor, significantly inhibited the release of 5-HT induced by methotrexate, but not by cisplatin, in a dose-dependent manner. When applied to isolated ileal tissues in vitro, nafamostat mesilate also significantly inhibited the release of 5-HT induced by methotrexate, but not by cisplatin, in a concentration-dependent manner. These results suggest that serine proteases are involved in the mechanism of the methotrexate-induced release of 5-HT from the rat small intestine.