Role of hippocampal TLR4 in neurotoxicity in mice following toluene exposure

The present study was designed to investigate the possible involvement of TLR4 pathway in the mouse hippocampus following toluene exposure. Male C3H/HeN and C3H/HeJ (TLR4 defective) mice were exposed to 0, 5, 50 or 500 ppm of toluene for 6 weeks. The expressions of TLR4-related signal transduction pathway mRNAs in the hippocampi were examined using real-time RT-PCR and an immunohistochemical analysis. In C3H/HeN mice, the relative mRNA expression levels of TLR4 and NF-κB activating protein were significantly up-regulated in the groups exposed to toluene, but not in the C3H/HeJ mice. Heat shock protein 70, a possible endogenous ligand for TLR4, mRNA was increased in the C3H/HeN mice exposed to toluene. This is the first report to show that TLR4 may have a role in the neurotoxic effects in mice exposed to toluene.     

Nanoparticle-rich diesel exhaust affects hippocampal-dependent spatial learning and NMDA receptor subunit expression in female mice

We investigated the effect of exposure to nanoparticle-rich diesel exhaust (NRDE) on hippocampal-dependent spatial learning and memory function-related gene expressions in female mice. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE), high-dose NRDE (H-NRDE) or filtered diesel exhaust (F-DE) for three months. A Morris water maze apparatus was used to examine spatial learning. The expression levels of the N-methyl-D-aspartate (NMDA) receptor subunit, proinflammatory cytokines and neurotrophin mRNAs in the hippocampus were then investigated using real-time RT-PCR. Mice exposed to H-NRDE required a longer time to reach the hidden platform and showed higher mRNA expression levels of the NMDA receptor subunit NR2A, the proinflammatory cytokine CCL3, and brain-derived neurotrophic factor (BDNF) in the hippocampus, compared with the findings in the control group. These results indicate that three months of exposure to NRDE affected spatial learning and memory function-related gene expressions in the female mouse hippocampus.     

Liver stiffness measurement versus clinicians' prediction or both for the assessment of liver fibrosis in patients with chronic hepatitis C

OBJECTIVES: The goal of this study was to estimate the additional value of liver stiffness measurement (LSM) with physicians' assessment of fibrosis based on epidemiological, clinical, and biological parameters. METHODS: One hundred forty-two unselected patients with chronic hepatitis C were included. Liver biopsy and LSM were performed simultaneously. First, four physicians (two junior residents with limited experience in hepatology and two senior hepatologists) independently predicted the stage of fibrosis according to the METAVIR classification, using clinical, epidemiological, and biological data. For the second step, they were informed of LSM values and could modify their first evaluation if necessary. Finally, the two successive evaluations were compared with the histological fibrosis score. RESULTS: Providing LSM values improved agreement between physicians and resulted in a better correlation between clinical impression and histological liver fibrosis. The diagnostic performances were only significantly improved with transient elastography for the diagnosis of cirrhosis where assessment improved in three of the four physicians (AUROC [area under receiver operating characteristic curve]: 0.76 vs 0.87, 0.80 vs 0.87, and 0.83 vs 0.89, all p < 0.05). Moreover, these performances were nearly similar for junior and senior physicians when LSM was provided with the AUROC ranging from 0.69 to 0.72 for significant fibrosis and 0.87 to 0.90 for cirrhosis. CONCLUSIONS: Providing LSM values to physicians results in a better estimation of liver fibrosis and a more accurate diagnosis of cirrhosis. Moreover, it allows physicians with limited experience to predict liver fibrosis as well as experienced hepatologists.     

Exposure to nanoparticle-rich diesel exhaust affects hippocampal functions in mice

Epidemiological studies have indicated associations between day-to-day particulate air pollution and increased risks of various adverse health outcomes. Although an association between exposure to diesel exhaust particles (DEPs) and the development of pulmonary inflammation has been reported, there are limited reports on the neurotoxic effects of DEPs, particularly those of nanoparticle-rich diesel exhaust (NRDE). In this minireview, we highlighted the effects of NRDE which was generated in the National Institute for Environmental Studies, on hippocampus-dependent spatial learning ability and the expression of memory-function-related genes, neurotrophins, and proinflammatory cytokines in a mouse model.     

Does early life toluene exposure alter the expression of NMDA receptor subunits and signal transduction pathway in infant mouse hippocampus?

We aim to investigate the critical window of susceptibility to toluene exposure during brain development and the effects of fetal and neonatal toluene exposure on the expression of N-methyl-d-aspartate (NMDA) receptor subunits and related transduction pathway in infant mice hippocampus. Pregnant mice (GD 14), male offspring (postnatal day; PND 2) or PND 8 were exposed to either a filtered air control (0 ppm), or 5, or 50 ppm of toluene for 6 h per day for 5 consecutive days. On PND 21, the expression levels of NMDA receptor subunits, cyclic AMP responsive element binding protein (CREB)-1, calcium/calmodulin-dependent protein kinase (CaMK)-IV, and apoptotic related genes (Bax, Bcl) mRNAs in the hippocampus were estimated using quantitative real-time RT-PCR and immunohistochemical analyses. NR2B, CaMKIV and CREB1 mRNAs increased significantly in the hippocampus of mice exposed to 50 ppm toluene on PND 2–6. In contrast, almost all memory function-related gene mRNAs and proapoptotic and anti-apoptotic ratio increased significantly in mice exposed to 5 or 50 ppm toluene on PND 8–12. However, mice exposed to toluene on GD 14–18 showed no significant change. Increased active caspase-3 immunoreactive cells were found in hippocampal CA1 area of PND 21 male mice exposed to 5 ppm toluene during PND 8–12. Our results suggest that late postnatal period may be a vulnerable and critical period to toluene exposure. Then, we have also examined the effect of toluene exposure in brain development on learning ability in young adult mice and found that poor spatial learning performance in PND 49 male mice exposed to 5 ppm toluene during critical period. This is the first study to show that the early toluene exposure induces persistent of the alteration of memory function-related genes in infant mice and memory deficit in later life via modulating the synaptic morphology and function.     

Protective effects of bifidobacterial adhesin on intestinal mucosa of stressed male rats via modulation of inflammation

This study aimed to assess BA impact on inflammation markers and repair of intestinal mucosa. Forty-eight rats were randomly divided into stress (n = 24) and BA (n = 24) groups. Stress was induced by fettering in all animals, fed enterally with 125.4 kJ/kg/d and 0.2 g/kg/d nitrogen. Then, rats were treated for 8 days with 5 mg/kg/d BA (BA group) or 5 mg/kg/d saline (Stress group). Levels of NF-κB, IL-10, TNF-α, and IFN-γ were measured at different time points, in plasma and intestinal mucosa samples. Changes in intestinal mucosa morphology were observed by electron microscopy. Plasma and/or mucosal levels of NF-κB, TNF-α, and IFN-γ were significantly higher in both groups after stress induction (P < 0.05). These high levels persisted in control animals throughout the experiment, and were significantly reduced in the BA group, 3 and 8 days after stress induction (P < 0.05). Interestingly, IL-10 levels were increased after BA treatment (P < 0.05). At day 8, ileal mucosal villi and crypt structure were significantly restored in the BA group. Bifidobacterial adhesin plays a role in repairing intestinal mucosa injury after stress by regulating the release of inflammatory mediators in the intestinal mucosa.     

Preliminary monitoring of concentration of particulate matter (PM<Subscript>2.5</Subscript>) in seven townships of Yangon City,Myanmar

Background

Airborne particulate pollution is more critical in the developing world than in the developed countries in which industrialization and urbanization are rapidly increased. Yangon, a second capital of Myanmar, is a highly congested and densely populated city. Yet, there is limited study which assesses particulate matter (PM_2.5) in Yangon currently. Few previous local studies were performed to assess particulate air pollution but most results were concerned PM₁₀ alone using fixed monitoring. Therefore, the present study aimed to assess distribution of PM_2.5 in different townships of Yangon, Myanmar. This is the first study to quantify the regional distribution of PM_2.5 in Yangon City.

Methods

The concentration of PM_2.5 was measured using Pocket PM_2.5 Sensor (Yaguchi Electric Co., Ltd., Miyagi, Japan) three times (7:00 h, 13:00 h, 19:00 h) for 15 min per day for 5 days from January 25^th to 29^th in seven townships. Detailed information of eight tracks for PM_2.5 pollution status in different areas with different conditions within Kamayut Township were also collected.

Results

The results showed that in all townships, the highest PM_2.5 concentrations in the morning followed by the evening and the lowest concentrations in the afternoon were observed. Among the seven townships, Hlaingtharyar Township had the highest concentrations (164 ± 52 μg/m³) in the morning and (100 ± 35 μg/m³) in the evening. Data from eight tracks in Kamayut Township also indicated that PM_2.5 concentrations varied between different areas and conditions of the same township at the same time.

Conclusion

Myanmar is one of the few countries that still have to establish national air quality standards. The results obtained from this study are useful for the better understanding of the nature of air pollution linked to PM_2.5. Moreover, the sensor which was used in this study can provide real-time exposure, and this could give more accurate exposure data of the population especially those subpopulations that are highly exposed than fixed station monitoring.

     

Impaired Lipid and Glucose Homeostasis in Hexabromocyclododecane-Exposed Mice Fed a High-Fat Diet

Background: Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear.Objectives: We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD).Methods: Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue.Results: In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice.Conclusions: Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity.Citation: Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect 122:277–283; http://dx.doi.org/10.1289/ehp.1307421     

Acute administration of toluene affects memory retention in novel object recognition test and memory function-related gene expression in mice

The present study was designed to investigate the acute effect of a single administration of toluene (300 mg kg^?1, i.p.) on memory retention in the hippocampus‐dependent novel object recognition test and N‐methyl‐D‐aspartate (NMDA) receptor subunit expression in the hippocampus of C3H/HeN female mice using real‐time RT‐PCR. We performed a novel object recognition test including a habituation phase, training phase and test phase in each mouse. Twenty‐four hours after the training phase, to determine the effect of acute toluene administration on memory retention, half of the mice (n = 10) were injected with toluene 60 min before the test phase. Toluene‐injected mice did not prefer novel objects and showed poor discrimination between novel and familiar objects and decreased expression of NMDA receptor subunit NR2B mRNA in the hippocampus. This is the first study to show that acute toluene injection impairs hippocampus‐dependent nonspatial memory retention accompanied by selective modulation of NMDA receptor subunit expression. Copyright © 2011 John Wiley & Sons, Ltd.