Coupling of neurons by electrical synapses (gap junctions) transiently increases in the mammalian CNS during development. We report here that the developmental increase in neuronal gap junction coupling and expression of connexin 36 (Cx36; neuronal gap junction protein) are regulated by an interplay between the activity of group II metabotropic glutamate receptors (mGluR) and GABAA receptors. Specifically, using dye coupling, electrotonic coupling, western blots and siRNA in the rat and mouse hypothalamus and cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs augments, and inactivation prevents, the developmental increase in neuronal gap junction coupling and Cx36 expression. However, changes in GABAA receptor activity have the opposite effects. The regulation by group II mGluRs is via cAMP/PKA-dependent signaling and by GABAA receptors is via Ca2+/PKC-dependent signaling. Further, the receptor-mediated up-regulation of Cx36 requires a neuron-restrictive silencer element in the Cx36 gene promoter and the down-regulation involves the 3′UTR of the Cx36 mRNA, as shown using RT-qPCR and luciferase reporter activity analysis. In addition, the MTT analysis indicates that mechanisms for the developmental increase in neuronal gap junction coupling directly control the death/survival mechanisms in developing neurons. Altogether, the results suggest a multi-tiered strategy for chemical synapses in developmental regulation of electrical synapses.

Skin aging occurs inevitably as a natural result of physiological changes over time. In particular, solar exposure of the skin accounts for up to 90% of skin damage. Numerous studies have examined the ability of dietary constituents to prevent skin aging, and recent research has emphasized the role of functional probiotics in intestinal function and skin aging. However, the mechanism of the interactions between aging and probiotics has not been elucidated yet. The aim of this study was to determine the role of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) identified as Lactobacillus plantarum HY7714 in regulating tight junctions in intestinal epithelial cells and increasing moisture retention in human dermal fibroblasts cells. We observed that HY7714 EPS controlled intestinal tight junctions in Caco-2 cells by upregulating the genes encoding occludin-1 (OCL-1) and zonula occluden-1 (ZO-1). In addition, HY7714 EPS effectively improved UVB-induced cytotoxicity and hydration capacity in HS68 cells by downregulating production of metalloproteinases (MMPs) and reactive oxygen species (ROS). In summary, HY7714 EPS is an effective anti-aging molecule in skin and may have therapeutic potential against skin diseases and UVB-induced damage. Therefore, HY7714 EPS serves as a functional substance in skin–gut axis communication.

Epidemiological studies have shown that exposure to particulate matter (PM) is associated with adverse health effects. Inhalation of fine particulate matter (PM2.5) is associated with elevated pulmonary diseases. However, the molecular mechanism underlying the initiation of lung inflammation following inhalation is unclear. In this study, we investigated the beneficial effects of two probiotics, Lactobacillus casei HY2782 and Bifidobacterium lactis HY8002, against PM-induced pulmonary inflammation. Model mice were subjected to chronic exposure of PM2.5. The results showed that PM2.5 enhanced oxidative stress and led to Th2 cytokine responses in the mice. PM2.5-exposed mice were orally administered with HY2782 and HY8002 from the day of first exposure to the end point of the study. The results showed that HY2782 ameliorated PM 2.5 exposure-enhanced leukocyte migration and activation of proinflammatory cytokines. HY2782 and HY8002 also prevented exacerbation of eosinophil and neutrophil infiltration in the bronchoalveolar lavage fluid. HY2782 and HY8002 significantly increased scavenging of PM2.5-induced reactive oxygen species and activated superoxide dismutase and catalase activity in the blood. These results indicate that the probiotics HY2782 and HY8002 protect against PM-induced pulmonary inflammation.

Obesity is a major health issue worldwide, and is associated with many diseases including type 2 diabetes. In this study, we evaluated the anti-obesity effects of combinations of two lactic acid bacteria (LAB), Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, and Cinnamomi Ramulus (CR) extract, and explored the mechanism through which they modulate gut microbiota using diet-induced obese mice. Male C57BL/6J mice were randomly divided into five groups that received a high-fat diet (HFD), HFD and LAB (HFD+LAB), HFD and CR extract (HFD+CR), HFD with LAB and CR extract (HFD+LAB+CR), or normal diet for 10 weeks. The mice in the HFD+LAB+CR group showed significant reductions in body weight gain, in particular epididymal fat and liver, blood leptin levels, and an increase in the levels of blood adiponectin. In addition, the LAB and CR extract altered the gut microbiota, mainly increasing the alpha diversity. These results demonstrate that a mixture of two LAB (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032) and CR extracts alleviate HFD-induced obesity, and has potential of being used as a strategy for the treatment of obesity.

Cudrania tricuspidata has been used as an East Asian folk remedy to treat various symptoms. Recently, scientific evidence of the efficacy of C. tricuspidata has emerged. The objective of this study was to elucidate protective role of C. tricuspidata in the gastric mucosa using pylorus-ligated Sprague-Dawley rats and primary parietal cells. C. tricuspidata ethanol extracts attenuated gastric mucosal damage, secretion, and juice acidity in pylorus-ligated rats; however, it did not affect expression of gastric acid-related genes [muscarinic acetylcholine receptor M3 receptor (M3R), histamine H2-receptors (H2R), and cholecystokinin-2/gastrin receptors (CCK2R)] or serum gastrin concentrations. Furthermore, extracts greatly reduced levels of gastric cyclic adenosine monophosphate (cAMP) and significantly increased mRNA levels of gastric-type mucins (MUC5AC and MUC6). To identify the mode of action of C. tricuspidata extract in regulating gastric acid secretion, intracellular cAMP and mRNA for H2R, M3R, and CCK2R were measured in primary parietal cells. mRNA levels of H2R, M3R, and CCK2R did not significantly differ following treatment with C. tricuspidata extract, whereas cAMP induced by the H2R-specific agonist was significantly decreased. C. tricuspidata may therefore reduce gastric acid secretion by inhibiting H2R activity rather than regulating mRNA expression. These finding suggest that ethanol extracts of C. tricuspidata inhibit H2R-related gastric acid secretion and increase gastric mucus to help prevent gastric mucosal damage. Therefore, C. tricuspidata extract has potential to be used in foods and medicines to prevent diseases related to gastric mucosal damage, such as gastritis and functional dyspepsia.