Dose Of Ethanol Research Articles

Altered Epigenetic Marks and Gene Expression in Fetal Brain, and Postnatal Behavioural Disorders, Following Prenatal Exposure of Ogg1 Knockout Mice to Saline or Ethanol.

Oxoguanine glycosylase 1 (OGG1) is widely known to repair the reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG), and more recently was shown to act as an epigenetic modifier. We have previously shown that saline-exposed Ogg1 -/- knockout progeny exhibited learning and memory deficits, which were enhanced by in utero exposure to a single low dose of ethanol (EtOH) in both Ogg1 +/+ and -/- progeny, but more so in Ogg1 -/- progeny. Herein, OGG1-deficient progeny exposed in utero to a single low dose of EtOH or its saline vehicle exhibited OGG1- and/or EtOH-dependent alterations in global histone methylation and acetylation, DNA methylation and gene expression (Tet1 (Tet Methylcytosine Dioxygenase 1), Nlgn3 (Neuroligin 3), Hdac2 (Histone Deacetylase 2), Reln (Reelin) and Esr1 (Estrogen Receptor 1)) in fetal brains, and behavioural changes in open field activity, social interaction and ultrasonic vocalization, but not prepulse inhibition. OGG1- and EtOH-dependent changes in Esr1 and Esr2 mRNA and protein levels were sex-dependent, as was the association of Esr1 gene expression with gene activation mark histone H3 lysine 4 trimethylation (H3K4me3) and gene repression mark histone H3 lysine 27 trimethylation (H3K27me3) measured via ChIP-qPCR. The OGG1-dependent changes in global epigenetic marks and gene/protein expression in fetal brains, and postnatal behavioural changes, observed in both saline- and EtOH-exposed progeny, suggest the involvement of epigenetic mechanisms in developmental disorders mediated by 8-oxoG and/or OGG1. Epigenetic effects of OGG1 may be involved in ESR1-mediated gene regulation, which may be altered by physiological and EtOH-enhanced levels of ROS formation, possibly contributing to sex-dependent developmental disorders observed in Ogg1 knockout mice. The OGG1- and EtOH-dependent associations provide a basis for more comprehensive mechanistic studies to determine the causal involvement of oxidative DNA damage and epigenetic changes in ROS-mediated neurodevelopmental disorders.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1β levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

A novel starch-based ethanol gel with contact-killing bacteria to cut off contact transmission of bacteria

The large-scale spraying of disinfectants has little effect on cutting off the contact transmission of bacteria, triggering a series of economic burdens and environmental pollution in public places. Herein, a novel multiscale starch-based ethanol gel (MSE) was prepared by shearing cassava starch at different temperatures and subsequently esterifying with oxalic acid to obtain multiscale pyranose esters (MPE), which targeted ethanol in a specific location to release only when human touched. Strong hydrogen bonding and nanoscale voids made MSE locking ethanol, and the destruction of this hydrogen bonding by water and pressure also promoted ethanol release to fingers. In terms of this, fingers could be sterilized by pressing MSE, especially when the pressure force on MSE was greater than 2.263 N, more than 95.76% of E. coli and S. aureus on fingers are inactivated. Meanwhile, compared with pure ethanol disinfectants and commercial ethanol gel, MSE reduced the ethanol dosage by 571 times and 225 times when kept sterile for three days in the same public area. Excellent adhesion and biocompatibility of MSE indicate that novel ethanol gel can be exerted to suppress contact transmission of bacteria in a practical and harmless way.

Striatonigral direct pathway 2-arachidonoylglycerol contributes to ethanol effects on synaptic transmission and behavior

Endocannabinoids (eCB) and cannabinoid receptor 1 (CB1) play important roles in mediating short- and long-term synaptic plasticity in many brain regions involved in learning and memory, as well as the reinforcing effects of misused substances. Ethanol-induced plasticity and neuroadaptations predominantly occur in striatal direct pathway projecting medium spiny neurons (dMSNs). It is hypothesized that alterations in eCB neuromodulation may be involved. Recent work has implicated a role of eCB 2-arachidonoylglycerol (2-AG) in the rewarding effects of ethanol. However, there is insufficient research to answer which cellular subtype is responsible for mediating the 2-AG eCB signal that might be involved in the rewarding properties of ethanol and the mechanisms by which that occurs. To examine the role of dMSN mediated 2-AG signaling in ethanol related synaptic transmission and behaviors, we used conditional knockout mice in which the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) was deleted in dMSNs, DGLαD1-Cre+. Using acute brain slice photometry and a genetically encoded fluorescent eCB sensor, GRABeCB2.0, to assess real-time eCB mediated activity of sensorimotor inputs from primary motor cortices (M1/M2) to the dorsolateral striatum, we showed that DGLαD1-Cre+ mice had blunted evoked eCB-mediated presynaptic eCB signaling compared to littermate controls. Furthermore, ethanol induced eCB inhibition was significantly reduced in DGLαD1-Cre+ deficient mice. Additionally, there was a reduction in the duration of loss of righting reflex (LORR) to a high dose of ethanol in the DGLαD1-Cre+ mice compared to controls. These mice also showed a male-specific decrease in ethanol preference accompanied by an increase in ethanol-induced water consumption in a voluntary drinking paradigm. There were no significant differences observed in sucrose and quinine consumption between the genotypes. These findings reveal a novel role for dMSN mediated 2-AG signaling in modulating ethanol effects on presynaptic function and behavior.

Coil-assisted ethanol embolotherapy for refractory head and neck arteriovenous malformations with Onyx recrudescence: 10-Year experiences

ObjectiveThis study aimed to evaluate the outcomes of coil-assisted ethanol embolotherapy in recanalized head and neck arteriovenous malformations (HNAVMs) with dilated outflowing veins after Onyx treatment. MethodsThirty-six patients with HNAVMs (18 females and 18 males with a mean age of 26.83 years) who experienced recurrence after Onyx embolization from October 2007 to October 2017 were included in this study. All patients underwent complete clinical and angiographic examinations. Further, each patient was classified based on the Schobinger stage before undergoing staged ethanol embolization. All patients were followed up for 5 years in-person at an interval of 3 months after discharge. The Kaplan-Meier method was used to perform the recurrence-free survival analysis. ResultsSixteen patients (44.4%) had Schobinger stage II HNAVMs, and the remaining patients had Schobinger stage III or IV (20/36 patients [55.6%]) HNAVMs. A total of 116 embolization procedures were performed, coils were applied in 107 procedures (92.2%) among patients with dilated outflowing veins. The dose of absolute ethanol was 16.39 mL per procedure in patients with Schobinger II HNAVMs, and 22.45 mL per procedure in patients with Schobinger III and IV HNAVMs (P = .024, 95% confidence interval, 1.128-5.009). During the 3-month evaluation, complete response was observed in 13 of 36 patients (36.1%), and partial response was observed in 23 of 36 patients (63.9%). The 5-year recurrence-free survival rate for patients who underwent Onyx treatment had improved 58.3% after ethanol embolization (95% confidence interval, 2.853-9.595; P < .0001). ConclusionsCoil-assisted ethanol embolotherapy could treat refractory HNAVMs with Onyx recrudescence effectively.

Assessing the effects of prenatal poly-drug exposure on fetal brain vasculature using optical coherence angiography.

Maternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development. We use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine. Ethanol (16.6% v/v, at a dose of ) and nicotine (at a dose of ) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: ) or nicotine (dose: ). While results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure. Results suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.

Quantitative understanding of the impact of stress factors on xylose fermentation at different high solid biomass loads

During lignocellulosic fermentation, cells are challenged by multiple stresses, leading to decreased performances, especially xylose conversion. Quantitatively understanding stress factors in alcoholic fermentation on xylose fermentation is prerequisite for designing and/or modifying lignocellulosic ethanol fermentation. Nonetheless, most studies only focus on just one type of stress, even only one target chemical compound, making it difficult to comprehensively understand the whole stress factors on xylose fermentation. In this study, stress factors in alcoholic fermentation of lignocellulosic hydrolysate were divided into five categories: inhibitors, fermentation metabolites, solid biomass residues, metal ions, and ethanol. Especially, extracted inhibitors, instead of target known inhibitors, were used for studying their effects on fermentation. The effects of each stress on xylose utilization were detailed investigated and compared. Principal component analysis was then performed for comprehensively analyzing effects of the above-mentioned five stresses on xylose fermentation. Results showed that high dose of ethanol is the most significant inhibition factor for xylose fermentation, followed by inhibitors and fermentation metabolites. Metal ions and solid biomass residues in hydrolysate have small effects on xylose fermentation. This study will provide fundamental theoretical support for designing efficient xylose conversion processes and constructing robust xylose-utilizing S. cerevisiae.

Potential and anion effects on the adsorption of 3′,4′-bis(hexylthio)-2,2′:5′,2′'-terthiophene on Au(1 1 1) electrode characterized by in situ STM

The adsorption of organic molecules on gold electrodes serves as a model to understand the organic/inorganic electrified interface, which is relevant to the study of molecular electronics and organic thin film semiconductors. Our previous study on terthiophene (TT) adsorption on an Au(111) electrode shows that immersing Au(111) crystals in a TT ethanol dosing solution installs an ordered TT adlayer on the sample. The current study addresses the adsorption of 3′,4′-bis(hexylthio)-2,2′:5′,2′'-terthiophene (DTDST), a molecule with a TT backbone attached with two thiolhexyl chains, on an ordered Au(111) electrode. High-quality STM images were obtained to reveal the internal and 2D spatial structures of DTDST admolecules. The potential greatly influenced the organization of DTDST on the ordered Au(111) electrode. Although the pristine DTDST adlayer was disordered, it transformed into ordered Au(111) - (3√3 × 9) and (5√3 × 26) structures after applying a potential more negative than 0 V (vs. Ag/AgCl) in 0.1 M H2SO4 and HClO4, respectively. Shifting the potential more positive than 0.25 V resulted in coadsorption of bisulfate anions and restructuring of the DTDST adlayer. High-quality molecular resolution STM images were collected to reveal the azimuthal orientation of the DTDST admolecule on the Au(111) electrode. The thiolhexyl chains of DTDST admolecules could arrange in such a way that allowed intermolecular van der Waals interactions. Oxidation of adsorbed DTDST molecules to yield oligomers was also revealed by in situ STM.

Embolo/sclerotherapy for the treatment of hand arteriovenous malformations: a single-center retrospective cohort experience.

To retrospectively report our preliminary experience of treating hand arteriovenous malformations (AVMs) with embolo/sclerotherapy. Retrospectively review the demographics, treatment detail, outcome data, and complications of 13 consecutive patients with hand AVMs from January 2018 to December 2021. We embolize the dominant outflow vein with elastic coils and then use absolute ethanol or polidocanol for intravascular sclerotherapy and bleomycin for interstitial sclerotherapy. Yakes type II presents in four lesions, type IIIa in six, and type IIIb in three. A total of 29 treatment episodes were conducted for the 13 patients (1 episode for 3 patients, 2 for 4 patients, and 3 for 6 patients; the repeated treatment rate was 76.9%). The mean stretched length of coils for 1 treatment episode was 95 cm. The mean absolute ethanol dosage was 6.8 ml (range 4-30 ml). In addition, 10 ml of 3% polidocanol foam was injected and interstitial sclerotherapy with 150,000 IU bleomycin was performed on every patient. The post-operative arterial-dominant outflow vein pressure index (AVI) increased in the 29 procedures (6.55 ± 1.68 vs. 9.38 ± 2.80, P < 0.05). The Mann-Whitney U test showed that the post-operative AVI was higher in patients without re-intervention (P < 0.05). Local swelling occurred after all the procedures. Blistering occurred in 6 of the patients in 13 (44.8%) of the 29 procedures. Superficial skin necrosis occurred in 3 of the patients in 5 (17.2%) of the 29 procedures. The swelling, blistering, and superficial skin necrosis recovered within 4 weeks. No finger amputation occurred. The follow-up time was 6 months. The 6-month assessment of clinical improvement after the last treatment episode showed that 2 patients were cured, 10 were improved, and 1 remained unchanged. With regard to angiographic evaluation, 9 showed partial response and 4 complete response. Embolo/sclerotherapy can be effective and safe for hand AVM. The AVI increased significantly after embolo/sclerotherapy, and the index may be valuable in predicting recurrence in further study.

ALCOHOLIC LIVER DISEASE: ISSUES OF ETIOLOGY AND THE IMPACT OF RISK FACTORS (LITERATURE REVIEW)

Alcohol consumption is one of the main causes leading to chronic liver disease. Alcoholic liver disease is a set of cascading events, consisting first of alcoholic hepatic steatosis and then mainly through alcoholic steatohepatitis, leading to cirrhosis and hepatocellular carcinoma. This review considers chronic alcohol intoxication as the main factor in the development of liver disease. Modern data on the prevalence of forms of alcoholic liver damage in Russia and in the world are presented. The role of the consumed dose of ethanol, the nature of the alcoholic beverage, as well as the pattern of alcohol consumption in the formation of liver damage is assessed, predisposing factors are presented. The leading risk factors for alcoholic liver damage are: female gender, hereditary predisposition (ethnicity), trophological status (underweight or obesity), taking certain hepatotoxic drugs, the amount and duration of alcohol consumption and the type of alcohol consumed, smoking. The presence of concomitant viral hepatitis, environmental toxico-ecological influence and prenatal intoxication also predispose to alcoholic liver damage. The article provides a detailed assessment of the role of the presented risk factors in the development of alcoholic liver damage. However, it is not possible to identify the dominant risk factor for alcoholic liver damage, since the development of liver pathology directly depends not only on the amount of alcohol consumed, but also on the individual combination of predisposing factors. Understanding the etiology of the disease and the contribution of modifiable risk factors to its development will allow the development of effective strategies aimed at reducing the incidence and mortality from liver diseases.

Dietary Alcohol Consumption Elicits Corneal Toxicity Through the Generation of Cellular Oxidative Stress.

Purpose: Clinical data suggest that alcohol use is associated with the development of signs and symptoms of dry eye disease. However, preclinical data investigating ocular toxicity after dietary alcohol consumption are lacking. In this study, we investigated the effects of alcohol on the ocular surface, in human corneal epithelial cells (HCE-T) in vitro and in C57BL/6JRj mice in vivo. Methods: HCE-T were exposed to clinically relevant doses of ethanol. To determine the effects of dietary alcohol consumption in vivo, wild-type mice were administered the Lieber-DeCarli liquid diet (5% vol/vol ethanol or isocaloric control) for 10 days ad libitum. Corneal fluorescein staining was performed to assess ocular surface damage. Histopathological and gene expression studies were performed on cornea and lacrimal gland tissue. Results: Sublethal doses of ethanol (0.01%-0.5%) resulted in a dose-dependent increase of cellular oxidative stress in corneal epithelial cells and a significant increase in NFE2L2 and downstream antioxidant gene expression, as well as an increase in NFκB signaling; short-term exposure (0.5%, 4 h) triggered significant corneal epithelial cell barrier breakdown. Exposure to the alcohol-containing diet caused a 3-fold increase in corneal fluorescein staining, with no effect on tear volumes. Corneal thickness was significantly reduced in the alcohol diet group, and corneal tissue revealed dysregulated antioxidant and NFκB signaling. Our data provide the first published evidence that alcohol exposure causes ocular toxicity in mice. Conclusions: Our results are consistent with clinical studies linking past alcohol consumption to signs of ocular surface disease.

Dynamic head loss in pilot- and full-scale wastewater sand filtration with phosphorus removal, denitrification, and associated bumping

Abstract Limitations of the operation of down-flow sand filters were investigated without and with dosages of methanol, ethanol, or acetate for denitrification and dosages of ferrous sulphate to remove phosphorous. The dynamic head loss was developed due to clogging by suspended solids (SS) that originated from the secondary sedimentation tanks including sludge overflow and from SS in primary settled wastewater that bypassed the biological step. The dynamic head loss was also developed from clogging by gas bubbles formed during denitrification, not by the SS produced from cell growth. The dynamic head loss in sand filters after 24 h operation without and with denitrification increased by 0.9–1.3 and 2.3–2.4 mH2O, respectively. The total time of operation was prolonged by 50% after one water bumping, by 75% after two bumpings, and by 85% after six or seven bumpings. Operational time for filter cycles was prolonged by 4–5 h by one bumping in the full-scale and pilot-scale filters. The time of operation depended on hydraulic loading. With a carbon source dosage, one filter cycle lasted 20–40 h at 10 m/h and 60 h at 5 m/h in pilot-scale filters, and 15–27 h at 3.3 m/h in full-scale filters.

Synergistic effects of combined treatment of 1,2-dichloroethane and high-dose ethanol on liver damage in mice and the related mechanisms.

Our previous studies have shown that the metabolism of 1,2-dichloroethane (1,2-DCE) mediated by CYP2E1 could result in oxidative damage in the liver of mice. In the current study, we further investigated the effects of combined treatment with 1,2-DCE and high dose ethanol on liver and the mechanisms since both of them can be metabolized by CYP2E1 in the liver. There are several novel findings in the current study. First, combined treatment of mice with 1,2-DCE and high-dose ethanol could synergistically upregulate both protein and mRNA levels of CYP2E1, which might aggravate liver damage through CYP2E1-mediated oxidative stress. Second, the combined treatment could also synergistically trigger NLRP3 inflammasome activation and inflammatory responses in the liver. Third, the combined treatment synergistically upregulated the antioxidant defence systems in response to oxidative stress, however the compensatory mechanisms of antioxidant defence systems appeared to be insufficient to protect liver damage in the mice. Finally, the upregulated CYP2E1 expression was confirmed by using its specific inhibitor to play the crucial roles in liver damage in the mice during the combined treatment.

Fucoidan mitigates gastric ulcer injury through managing inflammation, oxidative stress, and NLRP3-mediated pyroptosis

This study aimed to elucidate the gastro-protective effect of fucoidan against ethanol-induced gastric ulcer mediated via NLRP3-induced pyroptosis as an underlying mechanism, not yet assessed in prior research. Forty-eight male Albino mice were divided into six groups: Group I (normal control), group II (Ulcer/ethanol control), group III (Omeprazole + ethanol), group IV (fucoidan 25 mg + ethanol), group V (fucoidan 50 mg + ethanol) and group VI (fucoidan only). Fucoidan was administered orally for seven consecutive days followed by ulcer induction by a single oral dose of ethanol. Using colorimetric analysis, ELISA, qRT-PCR, histological assessment, and immunohistochemical studies, the results revealed that ethanol-induced ulcer exhibited an ulcer score of 42.5 ± 5.1 and a significant increase (p < 0.05) in malondialdehyde (MDA), nuclear factor kappa B (NF-κB), and interleukin 6 (IL-6) with a significant decrease in the gastro-protective mediators, prostaglandin E2 (PGE2), superoxide dismutase (SOD) and glutathione (GSH), accompanied with an increase in NLRP3, interleukin 1β (IL-1β), interleukin 18 (IL-18), caspase 1, caspase 11, gasdermin D, and toll-like receptor 4 (TLR4), compared with the normal control. Pre-treatment with fucoidan showed a comparable result with omeprazole. Additionally, pre-treatments elevated the levels of the gastro-protective mediators and lessened oxidative stress, relative to the positive control findings. Conclusively, fucoidan has a promising gastro-protective role by inhibiting inflammation and pyroptosis.

Impacts of maternal separation stress on ethanol-related responses, anxiety- and depressive-like behaviors in adolescent mice

The present work evaluated the consequences of chronic maternal separation (MS), an animal model of early-life stress, on ethanol intake and striatal Fos expression induced by ethanol consumption. Furthermore, we analyzed MS impacts on anxiety- and depressive-like behaviors and on locomotor and plasma corticosterone responses to intraperitoneal treatment with ethanol in adolescent mice. For that, male and female C57BL/6J mice were exposed or not to MS stress, for 3 h per day, from postnatal day (PND) 1 to 14, and submitted to behavioral tests from PND 28. In Experiment 1, MS and control groups of mice were submitted to an involuntary ethanol intake protocol, and striatal Fos expression following ethanol exposure was analyzed. In Experiment 2, mice behavior was assessed in elevated plus-maze, sucrose splash, saccharin preference, and open field tests. Locomotor and plasma corticosterone responses induced by a systemic dose of ethanol (1.75 g/kg) were also evaluated. Our results demonstrated that MS increased ethanol intake only in an acute manner and did not impact ethanol-induced Fos expression in the dorsal striatum and nucleus accumbens (NAc) core and shell subregions. MS did not change the parameters analyzed during elevated plus-maze, sucrose splash, preference for saccharin, and open field tests. MS did not affect locomotor activity following ethanol injection nor plasma corticosterone response to the drug. Thus, our data showed that MS transiently increased ethanol intake. However, early-life stress did not impact Fos, locomotor, or plasma corticosterone responses to the drug. In addition, MS did not affect anxiety- and depressive-like behaviors in adolescent mice.

G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice.

Sensitivity to ethanol provides an index of the predisposition to recover from unconsciousness induced by a dose of ethanol. The role of the G protein-coupled receptor 158 (GPR158) in modulating sensitivity to the sedative-hypnotic effect of ethanol has not been investigated. Loss of righting reflex (LORR) is a behavioral indicator of hypnosis in rodents. In this study, Gpr158-/- mice and wild-type (WT) littermates (n = 8/genotype) were tested using LORR induced by a dose of 3.5 g/kg ethanol, an open-field test (OFT), and a measure of blood ethanol concentration. The OFT was used to examine the role of GPR158 in the ethanol effect on motor activity in Gpr158-/- mice (n = 6/genotype). We also tested CamK2A-Cre;Gpr158fl/fl (n = 9) and Vgat-Cre;Gpr158fl/fl mice (n = 10) using the LORR test and OFT to compare with controls (n = 9 and 8, respectively). Gpr158 deficiency prolonged the LORR duration by 110.6%, t(14) = -5.241, p = 0.0001, without altering spontaneous activity, t(14) = -0.718, p = 0.485, or ethanol metabolism, F(1, 8) = 0.259, p = 0.625. Gpr158 knockout did not change the ethanol effect on locomotion, F(1, 10) = 0.262, p = 0.62. The LORR duration increased by 69% in the conditional knockouts of Gpr158 within calcium/calmodulin-dependent protein kinase II alpha-positive (CamK2A+ ) neurons, t(16) = -2.914, p = 0.01, and by 92% in the vesicular GABA transporter-positive (Vgat+ ) neurons, t(9.802) = -2.519, p = 0.023. Locomotion was not altered in Camk2A-Cre;Gpr158fl/fl , t(16) = 0.49, p = 0.631 or Vgat-Cre;Gpr158fl/fl mice, t(16) = 0.035, p = 0.972. This study reveals the key role of neuronal GPR158 in shaping sensitivity to the sedative-hypnotic effect of ethanol. These findings contribute to our understanding of the neurobiology of ethanol intoxication.

Highly Active Manganese Oxide from Electrolytic Manganese Anode Slime for Efficient Removal of Antibiotics Induced by Dissociation of Peroxymonosulfate.

In this paper, high-activity manganese oxide was prepared from electrolytic manganese anode slime to realize the efficient removal of antibiotics. The effects of sulfuric acid concentration, ethanol dosage, liquid-solid ratio, leaching temperature and leaching time on the leaching of manganese from electrolytic manganese anode slime were systematically studied. Under the optimal conditions, the leaching rate of manganese reached 88.74%. In addition, a Mn3O4 catalyst was synthesized and used to activate hydrogen persulfate (PMS) to degrade tetracycline hydrochloride (TCH). The synthesized Mn3O4 was characterized by XRD, XPS, Raman, SEM and HRTEM. As a result, the prepared Mn3O4 is spherical, with high purity and crystallinity. The catalytic activity of Mn3O4 for PMS to degrade TCH was increased to 82.11%. In addition, after four cycles, the performance remained at 78.5%, showing excellent stability and recyclability. In addition, O2- and 1O2 are the main active species in the degradation reaction. The activity of Mn3O4 is attributed to it containing Mn(II) and Mn(III) at the same time, which can quickly realize the transformation of high-valence and low-valence manganese, promote the transfer of electrons and realize the degradation of organic pollutants.

Developmental ethanol exposure has minimal impact on cerebellar microglial dynamics, morphology, and interactions with Purkinje cells during adolescence.

Fetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability, occurring in almost 5% of births in the United States. FASD lead to physical, behavioral, and cognitive impairments, including deficits related to the cerebellum. There is no known cure for FASD and their mechanisms remain poorly understood. To better understand these mechanisms, we examined the cerebellum on a cellular level by studying microglia, the principal immune cells of the central nervous system, and Purkinje cells, the sole output of the cerebellum. Both cell types have been shown to be affected in models of FASD, with increased cell death, immune activation of microglia, and altered firing in Purkinje cells. While ethanol administered in adulthood can acutely depress the dynamics of the microglial process arbor, it is unknown how developmental ethanol exposure impacts microglia dynamics and their interactions with Purkinje cells in the long term. To address this question, we used a mouse model of human 3rd trimester exposure, whereby L7cre/Ai9+/-/Cx3cr1G/+ mice (with fluorescently labeled microglia and Purkinje cells) of both sexes were subcutaneously treated with a binge-level dose of ethanol (5.0 g/kg/day) or saline from postnatal days 4-9. Cranial windows were implanted in adolescent mice above the cerebellum to examine the long-term effects of developmental ethanol exposure on cerebellar microglia and Purkinje cell interactions using in vivo two-photon imaging. We found that cerebellar microglia dynamics and morphology were not affected after developmental ethanol exposure. Microglia dynamics were also largely unaltered with respect to how they interact with Purkinje cells, although subtle changes in these interactions were observed in females in the molecular layer of the cerebellum. This work suggests that there are limited in vivo long-term effects of ethanol exposure on microglia morphology, dynamics, and neuronal interactions, so other avenues of research may be important in elucidating the mechanisms of FASD.

A History of Low-Dose Ethanol Shifts the Role of Ventral Hippocampus during Reward Seeking in Male Mice.

Although casual drinkers are a majority of the alcohol drinking population, understanding of the long-term effects of chronic exposure to lower levels of alcohol is limited. Chronic exposure to lower doses of ethanol may facilitate the development of alcohol use disorders, potentially because of ethanol effects on reward learning and motivation. Indeed, our previously published findings showed that chronic low-dose ethanol exposure enhanced motivation for sucrose in male, but not female, mice. As the ventral hippocampus (vHPC) is sensitive to disruption by higher doses of chronic ethanol and tracks reward-related information, we hypothesized that this region is impacted by low-dose ethanol and, further, that manipulating vHPC activity would alter reward motivation. In vivo electrophysiological recordings of vHPC population neural activity during progressive ratio testing revealed that vHPC activity was suppressed in the period immediately after reward seeking (lever press) in ethanol-naive controls, whereas suppression of vHPC activity anticipated reward seeking in ethanol-exposed mice. In both ethanol-naive and exposed mice, vHPC activity was suppressed before a reward magazine entry. Temporally selective inhibition of vHPC using optogenetics increased motivation for sucrose in ethanol-naive controls, but not in ethanol-exposed mice. Further, regardless of exposure history, vHPC inhibition promoted checking of the reward magazine, indicating a role for vHPC in reward tracking. There was no effect of chemogenetic inhibition of the vHPC either during training or testing on sucrose reward motivation. These results reveal novel ethanol-induced alterations in vHPC neural activity that shift how vHPC activity is able to regulate reward seeking.