Endotoxemia by Porphyromonas gingivalis Injection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose/Lipid Metabolism, and Alters Gut Microbiota in Mice

Many risk factors related to the development of non-alcoholic fatty liver disease (NAFLD) have been proposed, including the most well-known of diabetes and obesity as well as periodontitis. As periodontal pathogenic bacteria produce endotoxins, periodontal treatment can result in endotoxemia. The aim of this study was to investigate the effects of intravenous, sonicated Porphyromonas gingivalis (Pg) injection on glucose/lipid metabolism, liver steatosis, and gut microbiota in mice. Endotoxemia was induced in C57BL/6J mice (8 weeks old) by intravenous injection of sonicated Pg; Pg was deactivated but its endotoxin remained. The mice were fed a high-fat diet and administered sonicated Pg (HFPg) or saline (HFco) injections for 12 weeks. Liver steatosis, glucose metabolism, and gene expression in the liver were evaluated. 16S rRNA gene sequencing with metagenome prediction was performed on the gut microbiota. Compared to HFco mice, HFPg mice exhibited impaired glucose tolerance and insulin resistance along with increased liver steatosis. Liver microarray analysis demonstrated that 1278 genes were differentially expressed between HFco and HFPg mice. Gene set enrichment analysis showed that fatty acid metabolism, hypoxia, and TNFα signaling via NFκB gene sets were enriched in HFPg mice. Although sonicated Pg did not directly reach the gut, it changed the gut microbiota and decreased bacterial diversity in HFPg mice. Metagenome prediction in the gut microbiota showed enriched citrate cycle and carbon fixation pathways in prokaryotes. Overall, intravenous injection of sonicated Pg caused impaired glucose tolerance, insulin resistance, and liver steatosis in mice fed high-fat diets. Thus, blood infusion of Pg contributes to NAFLD and alters the gut microbiota

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Validation of Wistar-Kyoto rats kept in solitary housing as an animal model for depression using voxel-based morphometry

Abstract Major depressive disorder is a common psychiatric condition often resistant to medication. The Wistar-Kyoto (WKY) rat has been suggested as an animal model of depression; however, it is still challenging to translate results from animal models into humans. Solitary housing is a mild stress paradigm that can simulate the environment of depressive patients with limited social activity due to symptoms. We used voxel-based morphometry to associate the solitary-housed WKY (sWKY) rat model with data from previous human studies and validated our results with behavioural studies. As a result, atrophy in sWKY rats was detected in the ventral hippocampus, caudate putamen, lateral septum, cerebellar vermis, and cerebellar nuclei (p < 0.05, corrected for family-wise error rate). Locomotor behaviour was negatively correlated with habenula volume and positively correlated with atrophy of the cerebellar vermis. In addition, sWKY rats showed depletion of sucrose consumption not after reward habituation but without reward habituation. Although the application of sWKY rats in a study of anhedonia might be limited, we observed some similarities between the regions of brain atrophy in sWKY rats and humans with depression, supporting the translation of sWKY rat studies to humans

Photoelectrochemical Behavior of Self-Assembled Ag/Co Plasmonic Nanostructures Capped with TiO₂

The use of localized surface plasmon resonance induced by Ag nanostructures is a promising way for high-efficiency photoelectric conversion. In plasmonic photoelectric conversion devices, however, the chemical instability of Ag in ambient atmosphere and its immediate deterioration have been a critical issue. Here, we propose a Ag–Co nanostructure array embedded in a TiO₂ matrix as a plasmonic resonator that ensures long-term stability. We also developed an electrochemical process to remove surface Co nanoclusters protecting fresh Ag from exposure to air. This enabled us to “unseal” Ag at the desired time. Furthermore, we confirmed photoelectric conversion using Ag–Co–TiO₂ nanocomposite films in contact with solution; the photoelectric conversion was substantially enhanced by the plasmon resonance of the Ag nanorods. The Ag nanostructures sealed in a TiO₂ matrix are expected to be used in other application fields, such as catalytisis and sensing, in which a fresh Ag surface is needed

Effect of <i>Porphyromonas gingivalis</i> infection in the placenta and umbilical cord in pregnant mice with low birth weight

<p><b>Objective:</b> Growing evidence indicates an association between periodontitis and delivery outcome; however, the mechanism is unclear. This study aimed to investigate the influence of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) infection on delivery outcome in mice.</p> <p><b>Materials and methods:</b> Bacteremia was induced in pregnant Slc:ICR mice (8 weeks old) by intravenous injection of <i>Pg.</i> Mice were randomly divided into a control group (CO), and those receiving <i>Pg</i> injection at gestational day 1 (GD1), gestational day 15 (GD15) or every day (ED). Delivery outcome, <i>Pg</i> infection, and gene expression in the placenta and umbilical cord were evaluated.</p> <p><b>Results:</b> Birth weight was lower in the ED and GD15 groups than in the CO group. A remarkable increase in anti-<i>Pg</i> IgG antibody was observed in the ED and GD1 groups, although <i>Pg</i> was not detected in the placenta or umbilical cord. mRNA expression of <i>Tnfα</i> and <i>Il6</i> in the placenta, and <i>Hif1α</i> in the umbilical cord, was significantly increased in the ED group. Microarray analysis of the umbilical cord revealed increased expression of several genes including <i>Orm1</i>, <i>Mgl2</i>, <i>Rps6ka3</i> and <i>Trim15</i> in the ED group.</p> <p><b>Conclusions:</b><i>Pg</i> infection during the third trimester caused low birth weight and inflammation in the placenta and umbilical cord.</p