Exploring the Role of Glycine Metabolism in Coronary Artery Disease: Insights from Human Genetics and Mouse Models.

Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank.

Effect of Genetic and Dietary Perturbation of Glycine Metabolism on Atherosclerosis in Humans and Mice.

Objective: Epidemiological and genetic studies have reported inverse associations between circulating glycine levels and risk of coronary artery disease (CAD). However, these findings have not been consistently observed in all studies. We sought to evaluate the causal relationship between circulating glycine levels and atherosclerosis using large-scale genetic analyses in humans and dietary supplementation experiments in mice.

Adult mouse hippocampal transcriptome changes associated with long-term behavioral and metabolic effects of gestational air pollution toxicity.

Gestational exposure to air pollution increases the risk of autism spectrum disorder and cognitive impairments with unresolved molecular mechanisms. This study exposed C57BL/6J mice throughout gestation to urban-derived nanosized particulate matter (nPM). Young adult male and female offspring were studied for behavioral and metabolic changes using forced swim test, fat gain, glucose tolerance, and hippocampal transcriptome.

Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma.

Asthma is a chronic and genetically complex respiratory disease that affects over 300 million people worldwide. Here, we report a genome-wide analysis for asthma using data from the UK Biobank and the Trans-National Asthma Genetic Consortium. We identify 66 previously unknown asthma loci and demonstrate that the susceptibility alleles in these regions are, either individually or as a function of cumulative genetic burden, associated with risk to a greater extent in men than women.

Toxicity of urban air pollution particulate matter in developing and adult mouse brain: Comparison of total and filter-eluted nanoparticles.

Air pollution (AirP) is associated with many neurodevelopmental and neurological disorders in human populations. Rodent models show similar neurotoxic effects of AirP particulate matter (PM) collected by different methods or from various sources. However, controversies continue on the identity of the specific neurotoxic components and mechanisms of neurotoxicity.

Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease.

Background Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta-analysis of genome-wide association study data in up to 30 118 subjects of European ancestry.

Exposure to Nanoscale Particulate Matter from Gestation to Adulthood Impairs Metabolic Homeostasis in Mice.

Emerging evidence from epidemiological and animal studies suggests that exposure to traffic-related air pollutants and particulate matter less than 2.5 µm in diameter (PM) contributes to development of obesity and related metabolic abnormalities. However, it is not known whether nanoscale particulate matter (nPM) with aerodynamic diameter ≤200 nm have similar adverse metabolic effects.

Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo.

Background: Exposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution.

Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons.

Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5-μm diameter (PM). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy.

Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats.

In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures.

Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior.

Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two nonspecific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured by conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50-200 mg/kg, i.