Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat.

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague-Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12-14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.

Mating and social exposure induces an opioid-dependent conditioned place preference in male but not in female prairie voles (Microtus ochrogaster).

In rodents, sexual stimulation induces a positive affective state that is evaluated by the conditioned place preference (CPP) test. Opioids are released during sexual behavior and modulate the rewarding properties of this behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous species, in which copulation with cohabitation for 6h induces a pair bond. However, the mating-induced reward state that could contribute to the establishment of the long-term pair bond has not been evaluated in this species. The present study aimed to determine whether one ejaculation or cohabitation with mating for 6h is rewarding for voles. We also evaluated whether this state is opioid dependent. Our results demonstrate that mating with one ejaculation and social cohabitation with mating for 6h induce a CPP in males, while exposure to a sexually receptive female without mating did not induce CPP. In the female vole, mating until one ejaculation, social cohabitation with mating, or exposure to a male without physical interaction for 6h did not induce CPP. To evaluate whether the rewarding state in males is opioid dependent, the antagonist naloxone was injected i.p. The administration of naloxone blocked the rewarding state induced by one ejaculation and by social cohabitation with mating. Our results demonstrate that in the prairie vole, on the basis of the CPP in the testing conditions used here, the stimulation received with one ejaculation and the mating conditions that lead to pair bonding formation may be rewarding for males, and this reward state is opioid dependent.

A randomised controlled trial of a program based on the theory of planned behavior to promote fruit and vegetable intake among schoolchildren: PROFRUVE study protocol.

BACKGROUND: The PROFRUVE study is a controlled intervention based on the Theory of Planned Behavior (TPB), which follows those behavioral theories that have proved to be the most effective at changing infant fruit and vegetable (FV) intake pattern. The main purpose of the study is to evaluate the effectiveness of an intervention program in increasing FV consumption in schoolchildren aged 8 to 10 and based on TPB. METHODS: Eligible classrooms within schools from Vitoria-Gasteiz (Basque Country, Spain) will be randomly assigned to the intervention (classrooms n = 4; children n = 86) or control (classrooms n = 4; children n = 86) group. The intervention group will receive 14 sessions of 60 min during an academic year (October to June). These sessions, designed by a multidisciplinary team, are based on TPB and are directed at modifying determinants of behavior (attitudes, subjective norms, perceived behavioral control and intention of consumption), and intake of FV itself. Both the process and the evolution of consumption and determinants of behavior will be evaluated (before, during, shortly after and a year after) using validated surveys, 7 day food records, 24 h reminders and questionnaires. DISCUSSION: This study will provide a valid and useful tool to achieve changes in the consumption of FV at school level. A negative result will be helpful in redefining new strategies in the framework of changing habits in the consumption of FV. TRIAL REGISTRATION: This study has been retrospectively registered at ClinicalTrials.gov. Identifier: NCT03400891 . Data registered: 17/01/2018.

Observation of the (Λ)(7)He hypernucleus by the (e, e'K+) reaction.

An experiment with a newly developed high-resolution kaon spectrometer and a scattered electron spectrometer with a novel configuration was performed in Hall C at Jefferson Lab. The ground state of a neutron-rich hypernucleus, (Λ)(7)He, was observed for the first time with the (e, e'K+) reaction with an energy resolution of ~0.6 MeV. This resolution is the best reported to date for hypernuclear reaction spectroscopy. The (Λ)(7)He binding energy supplies the last missing information of the A = 7, T = 1 hypernuclear isotriplet, providing a new input for the charge symmetry breaking effect of the ΛN potential.

Application of Medical Information Systems for the detection of high risk patients: rapid care alerts. Pilot study of the ARA-Son Llàtzer Project.

OBJECTIVE: To describe the implementation of a Medical Information System (MIS) in the Critical Care Departament (CCD). DESIGN: A prospective observational cohort study was carried out. SETTING: Clinical and Surgical wards in Son Llàtzer Hospital. PATIENTS: Patients with criteria of rapid care alert (RCA) without treatment, cardiac arrest (CA), and unexpected ward deaths (UWD), during 2010. MAIN VARIABLES: Age, sex, nursing shift, nursing alert, vital signs, unplanned admission to intensive care, CA, UWD and death. RESULTS: The MIS detected 9647 episodes with RCA signs in 4020 patients (26.4 episodes/day). A total of 8547 episodes were reviewed. Sixty-five patients required rapid response by the intensive care staff; 61.5% were detected in the afternoon shift (15:00 a 22:00), and 61.5% were admitted to the CCD. Diminished consciousness (DC) and respiratory failure were the most frequent problems. The sepsis rate was 23%. We reviewed 45 CA and 35 UWD. Of the total cases of CA, 33 patients died (73.3%) and 66.7% had criteria of untreated RCA. Monitoring (P<.05) and rhythms amenable to defibrillation (P<.002) were associated to survival. As regards the UWD, 75% had criteria of untreated RCA, and 40.6% presented diminished consciousness. In the last 6 months there was a significant reduction in UWD (P=.01) CONCLUSIONS: The MIS could be a complimentary tool in the activity of the CCD to improve the prognosis of hospitalized patients.

Time of day of leaf wounding determines plant biomass and affects the interplay between growth and defence in Brassica crops.

Recent discoveries pointed out the importance of the mutual correlation between timing of environmental stress and plant fitness. However, the internal reshaping of plant growth under daily stress sensing, and their metabolic coordination remain to be investigated. Thus, we studied the connection between time of day, growth and defence to understand how plant fitness is affected by diurnal stress inputs. We examined if simulated herbivory (leaf wounding) in the morning, at midday or the evening differentially influence plant defence state vs growth in three crop species of Brassica: broccoli (Brassica oleraceae), turnip greens (B. rapa) and rapeseed (B. napus). The data revealed that plant's tolerance of wounding stress is diurnally regulated in Brassica crops. Trade-offs between biomass and investment in glucosinolates (GSL) and phenolics were affected by timing of leaf stress. Negative correlations between biomass and induction of defence compounds were found for plants treeated in the morning and evening. However, the correlations were positive for midday treatment. Interestingly, we revealed a new connection between plant growth and changes in aliphatic GSLs and flavonoids in response to wounding. These data suggest that metabolic stress-dependent circadian oscillations in leaf defences could be one mechanism conferring a competitive advantage to plants to anticipate daily environmental variations by synchronizing them with growth. Moreover, this work provides first insights into how secondary metabolites are linked to growth response in a timing-related manner.

New measurements of high-momentum nucleons and short-range structures in nuclei.

We present new measurements of electron scattering from high-momentum nucleons in nuclei. These data allow an improved determination of the strength of two-nucleon correlations for several nuclei, including light nuclei where clustering effects can, for the first time, be examined. The data also include the kinematic region where three-nucleon correlations are expected to dominate.

Chronic atrazine exposure increases the expression of genes associated with GABAergic and glutamatergic systems in the brain of male albino rat.

The herbicide atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is widely used to destroy grasses and broadleaf weeds in crops and some fruits. Studies in rodents have shown that acute, repeated or chronic exposure to ATR is associated with alterations in the nigrostriatal dopaminergic pathway, whereas its effects on GABAergic and glutamatergic pathways have only recently been reported. Sprague-Dawley male rats were exposed daily to 1 or 10 mg ATR/kg of BW for 13 months to evaluate the ATR effects on GABAergic and glutamatergic systems. At the end of the ATR treatment, the levels of mRNA of several genes involved in the production, vesiculation, reuptake, and receptors of GABA and Glu in the striatum (STR), nucleus accumbens (NAcc), prefrontal cortex (PFC), ventral midbrain (vMID) and hippocampus (HIPP) were evaluated by absolute qPCR. For the GABAergic genes, increased expression of GAD67 and Slc32a1 in STR and/or vMID in rats exposed to 1 and/or 10 mg ATR were detected. With regard to the expression of genes involved in the glutamatergic system, Slc17a6 and Grin1 in HIPP of rats exposed to 1 and/or 10 mg ATR, increased as was Gria1 in STR and PFC in the group exposed to 1 mg ATR. In the same fashion, Slc1a3 expression and MGLUR1 increased in STR of rats exposed to 1 and 10 mg ATR groups. The expression of the glutaminases gls (variants 1 and 2) was greater in STR, NAcc, HIPP, and PFC of rats exposed to 1 and/or 10 mg ATR. These findings show that the GABAergic and, especially glutamatergic systems are targets of ATR exposure.

Identification of genes related to germination in aged maize seed by screening natural variability.

Ageing reduces vigour and viability in maize inbred lines due to non-heritable degenerative changes. Besides non-heritable genetic changes due to chromosome aberrations and damage in the DNA sequence, heritable changes during maize conservation have been reported. Genetic variability among aged seeds of inbred lines could be used for association studies with seed germination. The objective of this study was to identify genes related to germination in aged seeds. The sweet corn inbred line P39 and the field corn inbred line EP44 were used as plant material. Bulks of living and dead seeds after 20 and 22 years of storage were compared by using simple sequence repeats (SSRs) and, when the bulks differed for a marker, the individual grains were genotyped. Differences between dead and living seeds could be explained by residual variability, spontaneous mutation, or ageing. Variability was larger for chromosome 7 than for other chromosomes, and for distal than for proximal markers, suggesting some relationships between position in the genome and viability in aged seed. Polymorphic SSRs between living and dead seeds were found in six known genes, including pathogenesis-related protein 2, superoxide dismutase 4, catalase 3, opaque endosperm 2, and metallothionein1 that were related to germination, along with golden plant 2. In addition, five novel candidate genes have been identified; three of them could be involved in resistance to diseases, one in detoxification of electrophillic compounds, and another in transcription regulation. Therefore, genetic variability among aged seeds of inbreds was useful for preliminary association analysis to identify candidate genes.

Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice.

Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.

A comparison between CLNA and CLA effects on body fat, serum parameters and liver composition.

The potential of conjugated linoleic acid (CLA) as an anti-obesity molecule for humans is still a matter for debate. Thus, a great deal of scientific work is focussed on the research of new effective molecules without deleterious effects on health. The aim of the present work was to analyse the effects of jacaranda seed oil, rich in a conjugated linolenic acid (CLNA), jacaric acid (cis-8,trans-10,cis-12), on body fat, serum parameters and liver composition in rats, and to compare these effects with those of trans-10,cis-12 CLA. Twenty-six male Wistar rats were divided into three groups fed with high-fat diets, supplemented or not (control group) with 0.5% trans-10,cis-12 CLA (CLA group) or 0.5% jacaric acid (CLNA group) for 7 weeks. No statistical differences in food intake or in final body weight were found. Whereas CLA reduced adipose tissue size, CLNA did not. Both CLA and CLNA significantly reduced non-HDL-cholesterol. In spite of a lack of significant changes in glucose and insulin levels, HOMA-IR index was significantly increased, as well as did non-esterified fatty acid levels in CLNA-fed rats. No changes in liver composition were observed. In conclusion, under our experimental conditions, jacaric acid, unlike CLA, does not show a body-fat lowering effect. Even though it leads to a healthy lipoprotein profile, it impairs insulin function. Consequently, it cannot be proposed as an anti-obesity molecule.

Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet.

Recently resveratrol, a compound naturally occurring in various plants, has been proposed as a potential anti-obesity compound. The aim of the present work was to analyse the effects of different doses of resveratrol on body fat and serum parameters in rats. Thirty-two male Sprague-Dawley rats were randomly divided into four groups and fed on a hypercaloric diet for 6 weeks. The doses oftrans-resveratrol used were 6, 30 and 60 mg/kg body weight/d in RSV1, RSV2 and RSV3 groups respectively. The stability of resveratrol when added to the diet was evaluated. Blood samples were collected, and white adipose tissue from different anatomical locations, interscapular brown adipose tissue, gastrocnemious muscles and liver were weighed. Commercial kits were used to measure serum cholesterol, glucose, triacylglycerols and non-esterified fatty acids. While the lowest dose did not have a body fat reducing effect, the intermediate dose reduced all the white adipose depots. The highest dose significantly reduced mesenteric and subcutaneous depots but not epididymal and perirenal tissues. Although the reduction in all the anatomical locations analysed was 19% in the RSV3 group, in the RSV2 group it was 24%. No significant differences among the experimental groups were found in brown adipose tissue, gastrocnemious muscle or liver weights. Serum parameters were not affected by resveratrol intake because no differences among the experimental groups were observed. These results suggest that resveratrol is a molecule with potential anti-obesity effect. The most effective of the three experimental doses was 30 mg/kg body weight/d.

Comparative metabolomics of temperature sensitive resistance to wheat streak mosaic virus (WSMV) in resistant and susceptible wheat cultivars.

In order to evaluate wheat resistance to wheat streak mosaic virus (WSMV) at low temperature and resistance breakdown at high temperature, metabolic profile of WSMV-resistant (R) and susceptible (S) wheat cultivars were analyzed. Metabolites were detected by UPLC-QTOF/MS in leaves of R and S plants challenged with WSMV at 20 °C and 32 °C, 24, 48 and 72 h post inoculation (hpi). WSMV and mock inoculated plants were used for discriminating the most significant metabolites and metabolic pathways affected at those temperatures. At 24 hpi/20 °C and 48 hpi/20 °C, the most important metabolites in R plants were coumarins, a limited number of lipids, and unknown compounds, while at 72 hpi/20 °C, in addition to coumarins, alkaloids and several amino acids were increased. Compared to 24 and 48 hpi, at 72hpi, in R plants most metabolic pathways were up-regulated at 20 °C. These resistance-related specific pathways included amino acid metabolism, lipid metabolism and alkaloids pathways. Also, several pathways were up-regulated at 32 °C.These combined heat stress and pathogen related pathways, included lipid metabolism and amino acid metabolism. Some carbohydrate metabolism pathways were considered as heat stress related pathways and could be associated with resistance breakdown. On the other hand, the increased expression of lipid compounds, especially 24 hpi at 32 °C in R plant, can be attributed to plant adaptation to combined stressors such as pathogen and high temperature. Increased susceptibility of R plants at 32 °C coincided with a down-regulated expression of components of signal transduction pathways or in a decreased level of metabolites related to this pathway, especially at a later time after infection, leading to decreased metabolite signaling. Decrease of signaling compounds under combined stress is a possible outcome of deactivating WSMV specific signaling networks leading to compatible response in R plants. The significance of these findings considering the recent increase of global temperature and the challenge of breakdown of temperature sensitive resistance to some plant viruses is discussed.

The inflammatory state of adipose tissue is not affected by the anti-inflammatory response of the A2a-adenosine system and miR-221/PTEN.

Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMI < 25 kg/m2 (BMI < 25) and BMI ≥ 25 kg/m2 (BMI ≥ 25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMI ≥ 25 compared to BMI < 25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue.

Adiposity and serum parameters in hamsters fed energy restricted diets supplemented or not with trans-10,cis-12 conjugated linoleic acid.

Numerous studies have demonstrated that conjugated linoleic acid (CLA) modulates body composition, reducing body fat accumulation in various mammalian species. However, very few studies have been carried out to assess the effect of CLA on previously stored body fat. The aim of the present work was to analyse the effectiveness of trans-10,cis-12 CLA in improving alterations produced by high-fat feeding in body fat and serum parameters when it was included in an energy-restricted diet. For this purpose male Syrian Golden hamsters were fed on high-fat diet for 7 weeks in order to increase their body fat content, and a further 25% energy-restricted diet supplemented or not with 0.5% trans-10,cis-12 CLA for 3 weeks. Adipose tissues, liver and gastrocnemious muscles were dissected and weighed. Adipocyte diameter and number were assessed in epididymal adipose tissue. Total cholesterol, triacylglycerols, non-esterified fatty acids and glucose were measured in serum. Three weeks of energy restriction resulted in a reduction in body weight and white adipose tissue size in all anatomical locations, without changes in liver and gastrocnemious muscle weights. Epididymal adipocyte size was reduced, but total adipocyte number remained unchanged. Serum cholesterol, triacylglycerols and glucose were significantly reduced. No differences were observed between the restricted groups (control and CLA supplemented). In conclusion, under our experimental conditions, the addition of trans-10,cis-12 CLA to the diet does not increase the benefits produced by energy restriction.

Behavioral effects and neuroanatomical targets of acute atrazine exposure in the male Sprague-Dawley rat.

Atrazine (ATR) is an herbicide broadly used in the world to control weeds in corn and sorghum fields, and it is potentially toxic for the dopaminergic system. Alterations in dopaminergic markers after ATR administration in rats and C57BL/6 mice have been reported. Behaviorally, it has been observed that ATR exposure causes hypoactivity shortly after its administration. To understand how acute ATR administration induces hypoactivity, we set out to map the brain areas responsive to ATR using c-Fos as a marker of neuronal activity, and tyrosine hydroxylase (TH) as a marker of dopaminergic neurons. The levels of glutamate and gamma-aminobutyric acid (GABA) were measured using high performance liquid chromatography, and spontaneous locomotor activity was evaluated as well. Male Sprague-Dawley rats received a systemic injection of 1% methyl cellulose (vehicle) or 100mg ATR/kg body weight to evaluate locomotor activity immediately after injection, c-Fos and TH immunohistochemistry in forebrain, midbrain and hindbrain, or glutamate and GABA content in various brain areas 90min after injection. To assess the possible involvement of the GABAergic system on ATR effects we tested the effects of a GABA-B antagonist. We found statistically significant decreases in locomotor activity, which were partially reversed by the GABA-B antagonist, and increases in the number of c-Fos-positive cells in thalamus, central amygdala, subthalamic nucleus, superior colliculus, and substantia nigra, TH positive cells were not selectively activated by ATR. The acute administration of ATR did not affect GABA or glutamate tissue levels but significantly decreased locomotor activity. These results corroborate the hypoactivity-inducing effect of ATR, and show that non-dopaminergic cells respond to the acute administration of ATR. The activation of cell populations in the basal ganglia and their target nuclei may contribute to the acute behavioral effects of ATR.

Effects of cis-9,trans-11 and trans-10,cis-12 CLA isomers on liver and adipose tissue fatty acid profile in hamsters.

The aim of the present study was to investigate the effect of cis-9,trans-11 and trans-10,cis-12 CLA on FA composition of TAG in epididymal adipose tissue and liver, and of hepatic phospholipids PL. Twenty-four Syrian Golden hamsters were randomly divided into three groups of eight animals each and fed semipurified atherogenic diets supplemented with either 0.5 g/100 g diet of linoleic acid or cis-9,trans-11 or trans-12,cis-9 CLA for 6 wk. Total lipids were extracted, and TAG and PL were separated by TLC. FA profile in lipid species from liver and adipose tissue, as well as in feces, was determined by GC. Trans-10,cis-12 CLA feeding significantly reduced linoleic and linolenic acids in TAG from both tissues, leading to reduced total PUFA content. Moreover, in the epididymal adipose tissue docosenoic and arachidonic acids were significantly increased. In liver PL, although no changes in individual FA were observed, total saturated FA (SFA) were decreased. No changes in TAG and PL FA profiles were induced by the cis-9,trans-11 CLA. TAG and PL incorporated cis-9,trans-11 more readily than trans-10,cis-12 CLA. This difference was not due to differential intestinal absorption, as shown by the analysis of feces. We concluded that only trans-10,cis-12 CLA induces changes in FA composition. Whereas increased PUFA content was observed in either liver or adipose tissue TAG, decreased SFA were found in liver PL. Incorporation of cis-9,trans-11 CLA in TAG is greater than that of trans-10,cis-12 CLA, but this is not due to differences in intestinal absorption.

Effects of trans-10,cis-12 conjugated linoleic acid on body fat and serum lipids in young and adult hamsters.

The aim of the present work was to determine whether t-10, c-12 conjugated linoleic acid (CLA) feeding was able to reduce body fat accumulation and improve the serum lipid profile in adult hamsters fed an atherogenic diet, in order to compare these effects with those observed in young growing hamsters. Young and adult hamsters were fed semi-purified atherogenic diets supplemented with 0.5 % linoleic acid or 0.5% t-10, c-12 CLA for 6 weeks. Body weight and food intake were measured every two days. Adipose tissue from different anatomical locations, liver and gastrocnemious muscle were dissected and weighed. Cholesterol, triacylglycerols, non-esterified fatty acids and proteins were determined spectrophotometrically and water content by gravimetry. In young hamsters, no significant differences were found in food intake, final body weight and gastrocnemious muscle weight. White adipose tissue weights were reduced, liver weight was increased and cholesterol and triacyl-glycerols in both serum and liver were reduced. In adult hamsters, CLA feeding decreased food intake and adipose tissue weights. No changes were observed in other parameters. The present study demonstrates that age has an influence in hamster responsiveness to t-10, c-12 CLA because, although when this isomer is added to an atherogenic diet it reduces body fat accumulation in both young and adults hamsters, the lessening of the effects on serum lipids brought about by atherogenic feeding is only observed in young animals. Moreover, it is clear that liver is a target for CLA in young but not in adult hamsters.

Effects of inorganic arsenic exposure on glucose transporters and insulin receptor in the hippocampus of C57BL/6 male mice.

Children and adolescent populations chronically exposed to high doses of inorganic arsenic (iAs) in drinking water in some regions around the world have shown behavioral and memory deficits. Recent studies have also associated iAs exposure with dysregulation of glucose metabolism. The hippocampus is a cerebral region well known for its role in learning and memory. Studies in vitro and in vivo have shown that the hippocampus is vulnerable to iAs exposure, and to changes in glucose metabolism. The glucose transporters (GLUTs) and insulin receptor (IR) regulate glucose metabolism in brain; they are expressed by hippocampal cells, and alterations in these proteins have been associated with memory deficits. The aims of this study were to evaluate the effects of iAs exposure via drinking water (DW) on GLUT1, GLUT3 and insulin receptor (INSR) mRNA expression in the hippocampus, on performance in a spatial memory task, and on peripheral glucose regulation. C57Bl/6 male mice were exposed to 50 mg iAs/L via DW for one, two, or three months. The qRT-PCR analyses indicated that, compared to a control group, GLUT1 and GLUT3 mRNA levels were decreased, while INSR mRNA levels were increased in the hippocampus of iAs exposed animals. The levels of iAs and its methylated species in the hippocampus of the iAs-exposed group were significantly higher than in controls. Mice exposed to iAs learned the spatial task but showed increased latency to find the submerged platform 48 h after the last training session; these animals also showed dysregulation of peripheral glucose. These results suggest that the effects of iAs exposure on a spatial memory task performance could be mediated by disruptions of glucose regulation in the CNS.

Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver.

Inorganic arsenic exposure via drinking water has been associated with cancer and serious injury in various internal organs, as well as with peripheral neuropathy and diverse effects in the nervous system. Alterations in memory and attention processes have been reported in exposed children, whereas adults acutely exposed to high amounts of inorganic arsenic showed impairments in learning, memory, and concentration. Glutathione (GSH) is extensively involved in the metabolism of inorganic arsenic, and both arsenite and its methylated metabolites have been shown to be potent inhibitors of glutathione reductase (GR) in vitro. Brain would be more susceptible to GR inhibition because of the decreased activities of superoxide dismutase (SOD) and catalase reported in this tissue. To investigate whether GR inhibition could be documented in vivo, we determined the activity and levels of GR in brain as well as in liver, the main organ of arsenic metabolism in mice exposed to 2.5, 5, or 10 mg/kg/day of sodium arsenite over a period of 9 days. In contrast to what has been observed in vitro, significant inhibition of the expression and activity of GR was observed only at the highest concentration used (10 mg/kg/day) in both organs. Although the disposition of arsenicals was higher in liver, significant amounts of inorganic and methylated arsenic forms were determined in the brain of exposed animals. The formation of monomethylarsenic (MMA) and dimethylarsenic (DMA) metabolites in the brain was confirmed by incubating brain slices for 24, 48, and 72 h with sodium arsenite.