Effects of Tarragon Hydroalcoholic Extract and Coumarin On Memory, Tissue Index and GABAA Receptor Gene Expression in The Hippocampus of Male Rats

Background and objective: Learning and memory are necessary for survival. The hippocampus plays a significant role in learning process. GABAA receptors in the hippocampus are effective in learning and memory mechanism. The present study effect of tarragon hydroalcoholic extract and coumarin on memory, tissue index and GABAA receptor gene expression in the hippocampus of male rats. Methodology: 56 Wistar rats were used and randomized in 7 groups (N = 8). These groups included the intact, receiving DMSO, receiving tarragon hydroalcoholic extract doses of 25, 50 and 100 mg/kg and receiving coumarin dose of 3, 5 mg/kg. They have undergone treatment intraperitoneally once a day for two weeks. The shuttle box was used for the memory retention test. The rats were killed according to the research ethical codes after the tests were done. When the brains of rats were removed, 4 brains in each group were chosen for the histological test using Nissl staining. In the other four brains, the hippocampus was removed immediately. The hippocampus was located in a microtube and was frozen by liquid nitrogen. Finally, a gene expression test was performed using real-time PCR. Results the findings of the present study reveal that there was no significant difference between of solvent recipients and the intact group in the memory retention test, the number of healthy hippocampal pyramidal neurons, and the expression of the GABAA gene. The treated groups with various doses of hydroalcoholic extract of tarragon and coumarin showed decreased in the memory retention test and the number of healthy pyramidals neurons as well as a significant increase in GABAA- α5 and GABAA- α2 genes expression compared to the group receiving solvent. Conclusion Tarragon hydroalcoholic extract and coumarin affects memory impairment through increasing the GABAA-α5 and GABAA-α2 genes expression and decreasing the number of healthy hippocampal neurons.

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.

Features of Neutrophils From Atopic and Non-Atopic Elite Endurance Runners

We collected peripheral blood from thirty-nine elite male endurance runners at rest (24 hours after the last exercise session) and used the Allergy Questionnaire for Athletes score and plasma specific IgE level to separate them into atopic and non-atopic athletes. Neutrophils obtained from atopic and non-atopic athletes were subsequently stimulated in vitro with fMLP (N-formyl-methionyl-leucyl-phenylalanine), LPS (lipopolysaccharide), or PMA (phorbol 12-myristate 13-acetate). Neutrophils from non-atopic runners responded appropriately to LPS, as evidenced by the production of pro (IL-8, TNF-α, and IL-6) and anti-inflammatory (IL-10) cytokines. Neutrophils from atopic elite runners exhibited lower responses to LPS stimulus as indicated by no increase in IL-1β, TNF-α, and IL-6 production. Neutrophils from non-atopic and atopic runners responded similarly to fMLP stimulation, indicating that migration function remained unaltered. Both groups were unresponsive to PMA induced reactive oxygen species (ROS) production. Training hours and training volume were not associated with neutrophil IgE receptor gene expression or any evaluated neutrophil function. Since non-atopic runners normally responded to LPS stimulation, the reduced neutrophil response to the stimuli was most likely due to the atopic state and not exercise training. The findings reported are of clinical relevance because atopic runners exhibit a constant decline in competition performance and are more susceptible to invading microorganisms.

Subgingival Microbiome and Specialized Pro-Resolving Lipid Mediator Pathway Profiles Are Correlated in Periodontal Inflammation

Failure of resolution pathways in periodontitis is reflected in levels of specialized pro-resolving lipid mediators (SPMs) and SPM pathway markers but their relationship with the subgingival microbiome is unclear. This study aimed to analyze and integrate lipid mediator level, SPM receptor gene expression and subgingival microbiome data in subjects with periodontitis vs. healthy controls. The study included 13 periodontally healthy and 15 periodontitis subjects that were evaluated prior to or after non-surgical periodontal therapy. Samples of gingival tissue and subgingival plaque were collected prior to and 8 weeks after non-surgical treatment; only once in the healthy group. Metabololipidomic analysis was performed to measure levels of SPMs and other relevant lipid mediators in gingiva. qRT-PCR assessed relative gene expression (2-ΔΔCT) of known SPM receptors. 16S rRNA sequencing evaluated the relative abundance of bacterial species in subgingival plaque. Correlations between lipid mediator levels, receptor gene expression and bacterial abundance were analyzed using the Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) and Sparse Partial Least Squares (SPLS) methods. Profiles of lipid mediators, receptor genes and the subgingival microbiome were distinct in the three groups. The strongest correlation existed between lipid mediator profile and subgingival microbiome profile. Multiple lipid mediators and bacterial species were highly correlated (correlation coefficient ≥0.6) in different periodontal conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to healthy controls revealed that one bacterial species, Corynebacterium durum, and five lipid mediators, 5(S)6(R)-DiHETE, 15(S)-HEPE, 7-HDHA, 13-HDHA and 14-HDHA, were identified in both conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to after treatment revealed that one bacterial species, Anaeroglobus geminatus, and four lipid mediators, 5(S)12(S)-DiHETE, RvD1, Maresin 1 and LTB4, were identified in both conditions. Four Selenomonas species were highly correlated with RvD1, RvE3, 5(S)12(S)-DiHETE and proinflammatory mediators in the periodontitis after treatment group. Profiles of lipid mediators, receptor gene and subgingival microbiome are associated with periodontal inflammation and correlated with each other, suggesting inflammation mediated by lipid mediators influences microbial composition in periodontitis. The role of correlated individual lipid mediators and bacterial species in periodontal inflammation have to be further studied.

Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?

Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.

Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning

Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.