Evaluation of estrogenic effects of municipal effluents to the freshwater mussel Elliptio complanata

Municipal effluents are an important source of estrogens to the aquatic environment. The purpose of this study was to examine the estrogenicity of municipal effluents to the indigenous freshwater mussel, Elliptio complanata. First, estradiol-binding sites in gonad homogenates were characterized to determine the binding affinity and specificity of estrogens. Mussels were exposed to increasing concentrations of a municipal effluent for 96 h at 15 degrees C. In another experiment, mussels were placed in cages and submerged for 62 days at 1.5 km upstream and 5 km downstream of a municipal effluent plume in the St. Lawrence River. Mussels were harvested for assessment of vitellogenin-like proteins in the hemolymph and determination of total lipid, carbohydrate and protein in the gonad. The presence of specific estrogen-binding sites was found in both male and female gonads. Binding of estradiol to cytosol proteins reached saturation, yielding a dissociation constant of 0.4 nM. Vitellogenin (Vg) levels increased significantly in both the hemolymph and the gonad after exposure to the effluent. Moreover, females appeared to be more sensitive than males to producing Vg. Mussels exposed in situ to contaminated surface waters had higher levels of Vg at the downstream site, again, females had higher levels of Vg than did males. On the other hand, lipid and sugar levels in male gonads were significantly increased at the downstream site. Moreover, mussels at the downstream site had decreased shell growth length and increased total and soft tissue weights. We conclude that municipal effluents contain bio-available xenoestrogens at levels sufficient to elicit effects in freshwater mussels.     

Adolescent exposure to anabolic/androgenic steroids and the neurobiology of offensive aggression: A hypothalamic neural model based on findings in pubertal Syrian hamsters

Considerable public attention has been focused on the issue of youth violence, particularly that associated with drug use. It is documented that anabolic steroid use by teenagers is associated with a higher incidence of aggressive behavior and serious violence, yet little is known about how these drugs produce the aggressive phenotype. Here we discuss work from our laboratory on the relationship between the development and activity of select neurotransmitter systems in the anterior hypothalamus and anabolic steroid-induced offensive aggression using pubertal male Syrian hamsters (Mesocricetus auratus) as an adolescent animal model, with the express goal of synthesizing these data into an cogent neural model of the developmental adaptations that may underlie anabolic steroid-induced aggressive behavior. Notably, alterations in each of the neural systems identified as important components of the anabolic steroid-induced aggressive response occurred in a sub-division of the anterior hypothalamic brain region we identified as the hamster equivalent of the latero-anterior hypothalamus, indicating that this sub-region of the hypothalamus is an important site of convergence for anabolic steroid-induced neural adaptations that precipitate offensive aggression. Based on these findings we present in this review a neural model to explain the neurochemical regulation of anabolic steroid-induced offensive aggression showing the hypothetical interaction between the arginine vasopressin, serotonin, dopamine, γ-aminobutyric acid, and glutamate neural systems in the anterior hypothalamic brain region.     

Effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on muscarinic, dopamine, and GABA receptors of the rat striatum

The effects of acute and chronic administration of diisopropylfluorophosphate (DFP) to rats on acetylcholinesterase (AChE) activity (in striatum, medulla, diencephalon, cortex, and medulla) and muscarinic, dopamine (DA), and gamma-aminobutyric acid (GABA) receptor characteristics (in striatum) were investigated. After a single injection of (acute exposure to) DFP, striatal region was found to have the highest degree of AChE inhibition. After daily DFP injections (chronic treatment), all brain regions had the same degree of AChE inhibition, which remained at a steady level despite the regression of the DFP-induced cholinergic overactivity. Acute administration of DFP increased the number of DA and GABA receptors without affecting the muscarinic receptor characteristics. Whereas chronic administration of DFP for either 4 or 14 days reduced the number of muscarinic sites without affecting their affinity, the DFP treatment caused increase in the number of DA and GABA receptors only after 14 days of treatment; however, the increase was considerably lower than that observed after the acute treatment. The in vitro addition of DFP to striatal membranes did not affect DA, GABA, or muscarinic receptors. The results indicate an involvement of GABAergic and dopaminergic systems in the actions of DFP. It is suggested that the GABAergic and dopaminergic involvement may be a part of a compensatory inhibitory process to counteract the excessive cholinergic activity produced by DFP.     

The effects of NMDA receptor antagonists on acute morphine antinociception in mice

Summary.  Antagonists of the N-methyl-d-aspartate (NMDA) receptor complex inhibit the development of tolerance to antinociceptive effects of morphine and upon acute administration, influence morphine antinociceptive activity. The analysis of numerous studies investigating acute interaction between NMDA receptor antagonists and morphine in mice indicate a variety of procedural differences and reveal that these compounds may potentiate, attenuate and produce no effect on morphine antinociception. The conditions responsible for such conflicting experimental outcome of acute interaction remain unclear. It appears that the effects of NMDA receptor antagonists on morphine tolerance are not causally related to their acute effects on morphine antinociception. Received July 6, 2001 Accepted August 6, 2001 Published online August 9, 2002     

The Differential Effect of Ischemia on the Active Uptake of Dopamine, γ-Aminobutyric Acid, and Glutamate by Brain Synap to somes

Abstract: Ischemic stroke was induced in the Mongolian gerbil by left common carotid ligation. No change in uptake of [³H]dopamine, [³H]γ-aminobutyric acid ([³H]GABA), or [¹⁴C]glutamate in synaptosomes obtained from the ischemic hemisphere was observed for up to 8 h. At 16 h after ligation, marked decrements in uptake were observed in animals showing hemiparesis: Uptake values expressed as a percent of the corresponding control hemisphere were 15.2% for dopamine, 28.0% for GABA, and 47.5% for glutamate. The differential sensitivity of dopamine terminals compared with glutamate terminals was highly significant. Separate experiments performed with synaptosomes isolated from the corpus striatum showed that the greater sensitivity to damage was intrinsic to the dopamine nerve terminal and not the result of regional variations in ischemic damage in brain. No bilateral effect of ischemia on dopamine uptake was evident. In animals exhibiting milder behavioral deficits (circling), a smaller and comparable decrement in uptake of dopamine, GABA, and glutamate was evident at 16 h, whereas animals not affected behaviorally showed no decrement at 16 h. Following uptake, the subsequent fractional release of neurotransmitter stimulated by 60 mM-potassium ions was not affected at any time point studied. Therefore, the loss in uptake at 16 h probably represents overt destruction of nerve terminals. Experiments with urethane used in place of pentobarbital for anesthesia during carotid occlusion showed that "protection" by pentobarbital was not a factor in the delayed response to ischemia. These results show that damage or destruction of nerve terminals is a delayed event following ischemia and that dopamine terminals are intrinsically more sensitive than glutamate terminals.     

Analgesic effects of dynorphin-A and morphine in mice

To investigate whether or not dynorphin-A is analgesic, the effect of this peptide was tested in comparison with that of morphine in mice. Dynorphin-A produced a potent analgesic effect in the acetic acid writhing and tail pinch tests, but a weak effect in the tail flick test when given by intracerebroventricular injection. In contrast, morphine caused a potent analgesia in all the tests. Dynorphin-A was more effective when given by intrathecal injection than by intracerebroventricular injection, whereas morphine was equipotent by both injection routes. The results suggest that dynorphin-A is analgesic and that its analgesia may be differentiated from that of morphine.     

Effects of Ischaemia on Neurotransmitter Release from the Isolated Retina

Abstract: The effects of "ischaemia" (glucose-free Krebs-bicarbonate medium gassed with N₂/CO₂ on the release of glutamate and other major neurotransmitters in the retina were examined using the isolated rat and rabbit retina. Amino acid transmitters, acetylcholine, and dopamine were measured by HPLC. The release of glutamate, aspartate, GABA, and glycine from ischaemic retinas was more than doubled after 30 min, and after 90 min of ischaemia the release of amino acids was ∼ 15–20-fold that of control values. Ischaemia also produced large increases in the release of dopamine from both the rat and especially the rabbit retina. In contrast, the release of acetylcholine from the rat retina was significantly decreased by ischaemia, although the release of choline was increased. Because the ischaemia-induced release of glutamate, aspartate, and GABA from the rat retina was completely Ca independent, and exposure of the retina to high K (50 m M ) did not stimulate amino acid release, it is concluded that the mechanisms underlying the ischaemia-induced release do not involve an initial release of K or an influx of calcium.     

Context-dependent effects of freshwater mussels on stream benthic communities

1. We asked whether unionid mussels influence the distribution and abundance of co‐occurring benthic algae and invertebrates. In a yearlong field enclosure experiment in a south‐central U.S. river, we examined the effects of living mussels versus sham mussels (shells filled with sand) on periphyton and invertebrates in both the surrounding sediment and on mussel shells. We also examined differences between two common unionid species, Actinonaias ligamentina (Lamarck 1819) and Amblema plicata (Say 1817). 2. Organic matter concentrations and invertebrate densities in the sediment surrounding mussels were significantly higher in treatments with live mussels than treatments with sham mussels or sediment alone. Organic matter was significantly higher in the sediment surrounding Actinonaias than that surrounding Amblema. Actinonaias was more active than Amblema and may have increased benthic organic matter through bioturbation. 3. Living mussels increased the abundance of periphyton on shells and the abundance and richness of invertebrates on shells, whereas effects of sham mussels were similar to sediment alone. Differences in the amount of periphyton growing on the shells of the two mussel species reflected differences in mussel activity and shell morphology. 4. Differences between living and sham mussel treatments indicate that biological activities of mussels provide ecosystem services to the benthic community beyond the physical habitat provided by shells alone. In treatments containing live mussels we found significant correlations between organic matter and chlorophyll a concentrations in the sediment, organic matter concentrations and invertebrate abundance in the sediment and the amount of chlorophyll a on the sediment and invertebrate abundance. There were no significant correlations among these response variables in control treatments. Thus, in addition to providing biogenic structure as habitat, mussels likely facilitate benthic invertebrates by altering the availability of resources (algae and organic matter) through nutrient excretion and biodeposition. 5. Effects of mussels on sediment and shell periphyton concentrations, organic matter concentrations and invertebrate abundance, varied seasonally, and were strongest in late summer during periods of low water volume, low flow, and high water temperature. 6. Our study demonstrates that freshwater mussels can strongly influence the co‐occurring benthic community, but that effects of mussels are context‐dependent and may vary among species.     

Evidence of feminization in wild Elliptio complanata mussels in the receiving waters downstream of a municipal effluent outfall

The endocrine-disrupting activity of municipal effluents has the potential to alter the reproductive system and induce feminization to aquatic organisms. The purpose of this study was to examine the sex ratio, vitellogenin (Vtg)-like proteins, serotonin, arachidonate cyclooxygenase (COX) activity and dopamine status in wild mussels living at sites upstream and downstream of two municipal effluent outfalls in the Mille-Îles River (Quebec, Canada). Gonad integrity was also studied by monitoring the gonado-somatic index (GSI), the activity of the rate-limiting enzyme aspartate transcarbamoylase (ATC) for purine synthesis, and changes in lipid peroxidation (LPO). The results showed that the proportion of females was dramatically increased from 30% at the upstream sites to 80% at the downstream sites. The levels of Vtg-like proteins were significantly elevated in the male mussels only. Male mussels downstream of the municipal effluent plumes expressed female-specific protein bands (Vtg-like), as determined by high-resolution gel electrophoresis and silver staining. The serotonin/dopamine ratio was significantly decreased in the downstream mussels, indicating that the gonad was in a state of early vitellogenesis. However, this change was not accompanied by changes in ATC, suggesting no significant egg production was underway; this was confirmed by the observation that the downstream mussels displayed significantly low GSIs. GSIs were rather dependent on the serotonin/dopamine ratio (r = 0.44; p < 0.001), while Vtg-like proteins were dependent on dopamine levels (r = 0.50; p < 0.001). The increase in COX activity at the downstream sites and its close relationship with increased serotonin levels suggest a concomitant serotonergic signalling in addition to VTG production. The production of Vtg-like proteins combined with the serotonergic effects of the municipal effluents was associated with oxidative damage (LPO) in the gonad. This study provides the first evidence of feminization in wild mussel populations and the disruption in gonad physiology by exposure to municipal effluents.     

Muscarinic Modulation of Striatal Dopamine, Glutamate, and GABA Release, as Measured with In Vivo Microdialysis

Abstract: Intrastriatal microdialysis was used to administer muscarinic drugs in freely moving rats for 40 min at a flow rate of 2 µl/min. Administration of the nonselective agonist pilocarpine at 10 m M increased striatal dopamine release and decreased extracellular GABA and glutamate overflow. Perfusion with the muscarinic M₂ antagonist methoctramine at 75 µ M increased extracellular dopamine and glutamate concentrations but exerted no changes on extracellular GABA levels. Intrastriatal administration of the M₁ antagonist pirenzepine at 0.05 µ M decreased extracellular dopamine overflow. Application of pirenzepine (0.05 and 5 µ M ) exerted no effects on the measured GABA or glutamate levels. There are thus important differences in applied doses of muscarinic drugs needed to obtain modulatory effects. High doses of agonists are probably needed to superimpose on the background of tonic influences of striatal acetylcholine, whereas antagonists can block the receptors in small doses. We further suggest that M₁ receptors might tonically facilitate striatal dopamine release, that M₂ receptors might tonically inhibit striatal glutamate efflux, and that acetylcholine does not exert tonic effects on striatal GABA release. The link with the pilocarpine animal model for temporal lobe epilepsy will be discussed.     

Pomegranate juice rescues developmental,neurobehavioral and biochemical disorders in aluminum chloride-treated male mice

PurposeAluminum (Al) is a harmful metal to organisms and is capable of entering the human body in multiple ways, such as through drinking, breathing, deodorant use, and vaccination. This study examined the prospective toxicity of Al and the protective attributes of pomegranate juice (PJ) on neurobehavioral and biochemical parameters of male mice.MethodsSix groups of male mice were treated for 35 days with 20 % PJ (group II), 40 % PJ (group III), 400 mg/kg Al (group IV), Al + 20 % PJ (group V), Al + 40 % PJ (group VI) or tap water (control, group I). Behavioral assessments were conducted for learning and memory evaluations at the end of experiment. In addition, the forebrain was isolated for biochemical analysis.ResultsThe exposure of male mice to Al decreased learning and memory retention in the shuttle box, Morris water-maze and T-Maze tests. Biochemical analysis revealed significant depletions in neurotransmitters including DA, 5-HT and AChE and oxidative proteins including GSH, GST, CAT and SOD and increased TBARES levels in Al-treated mice compared to untreated mice. Pomegranate juice provided protection against these effects after Al exposure by ameliorating learning and memory retention and oxidative state in a dose-independent manner.ConclusionOur data demonstrated that Al exposure caused behavioral and biochemical disorders. Pomegranate juice in lower dose has beneficial properties for health and can be used as a source of antioxidants to reduce the toxicity of Al and other substances.     

An analysis of GABA receptor changes in the discrete regions of mouse brain after acute and chronic treatments with morphine

Abstract: The effects of morphine on the affinity and distribution of GABA receptors in the mouse regions (striatum, medulla, diencephalon, cortex, and cerebellum) were investigated in relation to: (a) acute administration, (b) chronic administration (tolerance), (c) precipitated withdrawal by naloxone, an opiate antagonist, and (d) abrupt withdrawal for 8 and 24 h. The alterations in the affinity as reflected by the dissociation constant (K_D) and the number of receptors (B_max) in the synaptic membranes obtained from controls and various treatments were determined by radioligand binding assay using [³H]muscimol as a ligand. Significant changes were observed in striatum, medulla, and diencephalon, whereas other regions including whole brain exhibited marginal changes. In general the number of GABA receptors increased after tolerance development, which upon abrupt withdrawal returned to control levels except in the case of naloxone-induced precipitated withdrawal. The affinity changes in different regions were diverse in nature and were not evident in the whole brain membranes. These results indicate that: (a) the regional alterations in the affinity and distribution of GABA receptors may play a role in the induction, maintenance, and regression of morphine tolerance; (b) abrupt withdrawal and antagonist precipitated withdrawal affect the GABA system differently, (c) chronic morphine treatment appears to influence the GABA receptors in the cerebellum, a region generally known for its lack of opiate receptors.     

Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H2O2-induced cytotoxicity in PC12 cells

Aloe-emodin (AE) is one of the most important active components of Rheum officinale Baill. The present study aimed to investigate that AE could attenuate scopolamine-induced cognitive deficits via inhibiting acetylcholinesterase (AChE) activity and modulating oxidative stress. Kunming (KM) mice were received intraperitoneal injection of scopolamine (2 mg/kg) to induce cognitive impairment. Learning and memory performance were assessed in the Morris water maze (MWM). After behavioral testing, the mice were sacrificed and their hippocampi were removed for biochemical assays (superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), AChE and acetylcholine (ACh)). In vitro, we also performed the AChE activity assay and H₂O₂-induced PC12 cells toxicity assay. After 2 h exposure to 200 μM H₂O₂ in PC12 cells, the cytotoxicity were evaluated by cell viability (MTT), nitric oxide (NO)/lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) production. Our results confirmed that AE showed significant improvement in cognitive deficit in scopolamine-induced amnesia animal model. Besides, it increased SOD, GPx activities and ACh content, while decreased the level of MDA and AChE activity in AE treated mice. In addition, AE was found to inhibit AChE activity (IC₅₀ = 18.37 μg/ml) in a dose-dependent manner. Furthermore, preincubation of PC12 cells with AE could prevent cytotoxicity induced by H₂O₂ and reduce significantly extracellular release of NO, LDH and intracellular accumulation of ROS. The study indicated that AE could have neuroprotective effects against Alzheimer’s disease (AD) via inhibiting the activity of AChE and modulating oxidative stress.     

Endogenous Dopamine Increases Extracellular Concentrations of Glutamate and GABA in Striatum of the Freely Moving Rat: Involvement of D1 and D2 Dopamine Receptors

Interactions between endogenous dopamine, glutamate, GABA, and taurine were investigated in striatum of the freely moving rat by using microdialysis. Intrastriatal infusions of the selective dopamine uptake inhibitor nomifensine (NMF) were used to increase the endogenous extracellular dopamine. NMF produced a dose-related increase in extracellular dopamine and also increased extracellular concentrations of glutamate, GABA, and taurine. Extracellular increases of dopamine were significantly correlated with extracellular increases of glutamate and GABA, but not taurine. To investigate whether the increased extracelular dopamine produced by NMF was responsible for the concomitant increase of glutamate and GABA, D1, and D2 receptor antagonists were used. Dopamine receptor antagonists D1 (SCH23390) and D2 (sulpiride) significantly attenuated the increases of glutamate and GABA produced by NMF. These data suggest that endogenous dopamine, through both D1 and D2 dopamine receptors, plays a role in releasing glutamate and GABA in striatum of the freely moving rat.     

Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes

Worldwide population is aging, and a large part of the growing burden associated with age-related conditions can be prevented or delayed by promoting healthy lifestyle and normalizing metabolic risk factors. However, a better understanding of the pleiotropic effects of available nutritional interventions and their influence on the multiple processes affected by aging is needed to select and implement the most promising actions. New methods of analysis are required to tackle the complexity of the interplay between nutritional interventions and aging, and to make sense of a growing amount of -omics data being produced for this purpose. In this paper, we review how various systems biology-inspired methods of analysis can be applied to the study of the molecular basis of nutritional interventions promoting healthy aging, notably caloric restriction and polyphenol supplementation. We specifically focus on the role that different versions of network analysis, molecular signature identification and multi-omics data integration are playing in elucidating the complex mechanisms underlying nutrition, and provide some examples on how to extend the application of these methods using available microarray data.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0508-9) contains supplementary material, which is available to authorized users.     

Multiple molecular and neuropharmacological effects of MDMA (Ecstasy)

3,4-Methylenedioxymethamphetamine (MDMA), commonly referred to as Ecstasy, is a widely abused, psychoactive recreational drug, which induces short- and long-term neuropsychiatric behaviors. This drug is neurotoxic to serotonergic neurons in vivo, and induces programmed cell death in cultured human serotonergic cells and rat neocortical neurons. Over the years it has been shown that MDMA alters the release of several neurotransmitters in the brain, it induces recompartmentation of intracellular serotonin and c-fos, and modifies the expression of a few genes. Recently, we observed changes in gene expression in mice treated with MDMA, and cloned and sequenced 11 cDNAs thus affected (4 correspond to known and 7 to unknown genes). The effect of MDMA on two of these genes, GABA transporter 1 and synaptotagmin IV was studied in detail. Characterization of the relationship between a given gene and certain physiological or behavioral effects of MDMA could shed light on the mechanism of the drug's action. However, establishing such a connection is difficult for several reasons, including that serotonergic neurons are not the only cells affected by MDMA. In this review, molecular and neurochemical events that occur in the brain following exposure to MDMA, and link between the observed molecular changes with known physiological effects of the drug are discussed. It is indicated that MDMA alters the expression of several proteins involved in GABA neurotransmission, thus having critical effect on thermoregulation and MDMA acute toxicity. This analysis should facilitate development of novel approaches to prevent deleterious effects, especially mortality induced by MDMA and other abused psychostimulants.     

Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions

We investigated whether water extract of Brazilian green propolis (WEP) and its main constituents [caffeoylquinic acid derivatives (3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, chlorogenic acid) and cinnamic acid derivatives (p-coumaric acid, artepillin C, drupanin, baccharin)] exert neuroprotective effects against the retinal damage induced by oxidative stress. Additionally, their neuroprotective effects were compared with their antioxidant effects. WEP, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, chlorogenic acid, and p-coumaric acid (but not artepillin C, baccharin, or drupanin) concentration-dependently inhibited oxidative stress-induced neurotoxicity [achieved using L-buthionine-(S,R)-sulfoximine (BSO) to deplete glutathione in combination with glutamate to inhibit cystine uptake] in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus). At their effective concentrations against oxidative stress-induced retinal damage, WEP, 3,4-di-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, and chlorogenic acid (but not cinnamic acid derivatives) inhibited lipid peroxidation (LPO) in mouse forebrain homogenates. Thus, the neuroprotective effects of WEP and caffeoylquinic acid derivatives paralleled those against LPO. These findings indicate that WEP and caffeoylquinic acid derivatives have neuroprotective effects against retinal damage in vitro, and that these effects may be partly mediated via antioxidant effects.     

The effects of zinc oxide nanoparticles on the metallome in freshwater mussels

The use of zinc oxide nanoparticles (nanoZnO) as sunscreens has raised concerns about their safety and release in the aquatic environment through swimming activities and within municipally treated wastewaters. This study's purpose was to examine the effects of nanoZnO on the elemental composition (metallome) in exposed freshwater mussels, Elliptio complanata. Mussels were exposed for 21 days to an environmentally realistic (low) concentration (2 μg/L) of nanoZnO and zinc chloride. The mussels were also exposed to a physically and chemically treated municipal effluent (ME), both alone and in the presence of both forms of Zn. The metallome profile was characterized by the following 15 elements in gills, digestive gland and gonad tissues: Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, V and Zn. The levels of metallothioneins (MT) and lipid peroxidation (LPO) in the digestive gland were also measured as biomarkers of toxic effects. The data revealed that exposure to nanoZnO increased the total levels of Zn, MT and LPO in the digestive gland. Discriminate function analysis revealed that the digestive gland responded the most to exposure to either nanoZnO or Zn^2 +. For nanoZnO, the observed changes in Al, As and Mo in the digestive gland offered the best discrimination from dissolved Zn^2 +. Co-exposure of nanoZnO with the ME changed the metallome profile closer to dissolved Zn^2 +, suggesting a common interaction site within the ME. This was observed in changes in Ni, Cu, Se and Zn in the digestive gland of exposed mussels. Canonical analysis of essential and non-essential elements revealed that exposure to nanoZnO increased the relationships between LPO and the sum of essential elements in the digestive gland. Conversely, exposure to dissolved Zn^2 + and the ME decreased the relationship between the sum of non-essential elements and LPO and MT. In conclusion, the use of a “metallomic” approach was used to discriminate changes following exposure to nanoZnO and dissolved Zn in freshwater mussels and provided insights into the interaction of forms of Zn in ME towards mussels.     

Prenatal and early life arsenic exposure induced oxidative damage and altered activities and mRNA expressions of neurotransmitter metabolic enzymes in offspring rat brain

To better understand the effect of arsenic on central nervous system by prenatal and early life exposure, the oxidative stress and neurotransmitter metabolic enzymes were determined in offspring rats' brain cortex and hippocampus. Forty‐eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO₂ from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic (As)‐containing water as the dams. The level of malondialdehyde in 100 mg/L As‐exposed pup's brain on PND 0 and cortex on PND 28 and 42 were significantly higher than in the control group (p < 0.05). Reduced glutathione (GSH) levels showed a clear decreasing trend in pup's cortex and hippocampus on PND 42. Activity of acetylcholinesterase was significantly higher in 100 mg/L As‐exposed pup's hippocampus than in control group on PND 28 and 42. mRNA expression of glutamate decarboxylase (GAD₆₅ and GAD₆₇) in 100 mg/L As‐exposed pup's cortex or hippocampus on PND 28 and 42 were significantly higher than in control (p < 0.05). These alterations in the neurotransmitters and reduced antioxidant defence may lead to neurobehavioral and learning and memory changes in offspring rats. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:368–378, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20349