Here, we focused on the hippocampus as this structure is generally thought to be affected only in manifest HD despite the subtle cognitive deficits known to emerge in prodromal HD. We used super-resolution microscopy and multi-electrode array electrophysiology as sensitive measures of excitatory synapse structure and function, respectively, in the hippocampus of presymptomatic heterozygous HD mice (Q175FDN model). We found clear evidence for enhanced AMPA receptor subunit clustering and hyperexcitability well before the onset of a detectable HD-like behavioral phenotype. In addition, activity-dependent re-organization of synaptic protein nanostructure, and functional measures of synaptic plasticity were impaired in presymptomatic HD mice. These data demonstrate that synaptic abnormalities in the presymptomatic HD brain are not exclusive to the striatum, and highlight the need to better understand the region-dependent complexities of early synaptopathy in the HD brain.The present study was performed to determine the acute toxicity of sodium laureth sulfate (SLES) and its sublethal effects on oxidative stress enzymes in benthic oligochaete worm Tubifex tubifex. The results showed that 96 h median lethal concentration (LC50) value of SLES for Tubifex tubifex is 21.68 mg/l. Moreover exposed worms showed abnormal behaviours including incremented erratic movement, mucus secretion, and decreased clumping tendency at acute level. Percentage of autotomy additionally increased significantly (P less then 0.05) with the increasing dose of toxicant at 96 h exposure. Sublethal concentrations of SLES (10% and 30% of 96 h LC50 value) caused paramount alterations in the oxidative stress enzymes. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GPx) exhibited a striking initiatory increment followed by a resulting descending pattern. Moreover, during exposure times, catalase (CAT) activity and malondialdehyde (MDA) level increased markedly with incrementing concentrations of SLES. However, the effects of sodium laureth sulfate on Tubifex tubifex were characterized and portrayed by the development of a correlation matrix and an integrated biomarker response (IBR) assessment. These results indicate that exposure to this anionic surfactant alters the survivability and behavioral response at acute level and modifies changes in oxidative stress enzymes at sublethal level in Tubifex tubifex.Mitochondria produce and scavenge reactive oxygen species (ROS); however, whether oxidative distress due to exogenous stress arises from excessive production or impaired scavenging remains unclear. selleck chemicals We assessed the effect of copper (Cu) and thermal stress on kinetics of ROS (H2O2) consumption in mitochondria isolated from fish heart. Mitochondria were energized with succinate, glutamate-malate or palmitoylcarnitine (PC) and incubated with 1-25 μM Cu at 11 (control) and 23 °C. We found that H2O2 consumption capacity of heart mitochondria varies with substrate and is additively reduced by temperature rise and Cu. While Cu is a potent inhibitor of H2O2 consumption in mitochondria oxidizing glutamate-malate and succinate, mitochondria oxidizing PC are resistant to the inhibitory effect of the metal. Moreover, the sensitivity of H2O2 consumption pathways to Cu depend on the substrate and are greatly impaired during oxidation of glutamate-malate. Pharmacological manipulation of mitochondrial antioxidant systems revealed that NADPH-dependent peroxidase systems are the centerpieces of ROS scavenging in heart mitochondria, with the glutathione-dependent pathway being the most prominent while catalase played a minimal role. Surprisingly, Cu is as efficacious in inhibiting thioredoxin-dependent peroxidase pathway as auranofin, a selective inhibitor of thioredoxin reductase. Taken together, our study uncovered unique mechanisms by which Cu alters mitochondrial H2O2 homeostasis including its ability to inhibit specific mitochondrial ROS scavenging pathways on a par with conventional inhibitors. Importantly, because of additive inhibitory effect on mitochondrial ROS removal mechanisms, hearts of organisms jointly exposed to Cu and thermal stress are likely at increased risk of oxidative distress. Previous studies showed that artemisinin (ART) may be useful in the protection against the early development of atherosclerosis, but the effects of ART on vasodilation and eNOS remained unclear. In the current study, we investigated the protective effect of ART on endothelial cell injury induced by oxidative stress and its underlying mechanism via MTT assay, Flow Cytometry Assay, Vasodilation study, Western blotting and vivo assay. We found that pretreatment of human umbilical vein endothelial cells (HUVECs) with ART significantly suppressed H2O2-induced cell death by decreasing the extent of oxidation and MDA activity, activating SOD, increasing NO production and inhibiting caspase 3/7 activity. Meanwhile, we also found that ART was able to activate PI3K/Akt/eNOS pathway. PI3K inhibitor LY294002 or Akt kinase specific inhibitor Akt inhibitor VIII blocked the protective effect of ART. To explore the effect of ART in the damage of vasodilation induced by H2O2 in mice, we treated the aortic ring from C57BL/6 mice with H2O2 with or without ART, the results demonstrated that ART ameliorated endothelium-dependent vasodilation damage induced by H2O2. Taken together, these data suggest that ART is able to protect endothelial function and vasodilation from oxidative damage, at least in part through activation of PI3K/Akt/eNOS pathway. Our findings indicate that artemisinin maybe as a potential therapeutic agent for patients with atherosclerosis.Taken together, these data suggest that ART is able to protect endothelial function and vasodilation from oxidative damage, at least in part through activation of PI3K/Akt/eNOS pathway. Our findings indicate that artemisinin maybe as a potential therapeutic agent for patients with atherosclerosis.Inflammation and immune mechanisms are believed to play important roles in Alzheimer's disease pathogenesis. Research supports the link between poor oral health and Alzheimer's disease. Periodontal disease and dental caries represent the two most common infections of the oral cavity. This study focused on a precursor to Alzheimer's disease, mild cognitive impairment (MCI). Using 16S rRNA sequencing, we characterized and compared the oral microbiome of 68 older adults who met the criteria for MCI or were cognitively normal, then explored relationships between the oral microbiome, diagnostic markers of MCI, and blood markers of systemic inflammation. Two taxa, Pasteurellacae and Lautropia mirabilis were identified to be differentially abundant in this cohort. Although systemic inflammatory markers did not differentiate the two groups, differences in five cerebrospinal fluid inflammatory mediators were identified and had significant associations with MCI. Because inflammatory markers may reflect CNS changes, pursuing this line of research could provide opportunities for new diagnostic tools and illuminate mechanisms for prevention and mitigation of Alzheimer's disease.