Toxicity and effects of copper oxide nanoparticles on cognitive performances in rats.

There is increasing scientific evidences that the physical and chemical properties of manufactured nanoparticles lead to an increase in their bioavailability and toxicity. Among them Copper oxide nanoparticles (CuO-NPs) are widely used in different fields. However their potential adverse effects namely on brain functions are still discussed. Thus, the present study aimed to investigate the subacute oral toxicity and effects of CuO-NPs on cognitive performances in rats. Rats were randomly divided into three groups of 8 animals each, a control group received a dose 9‰ sodium chloride and the other groups received a suspension of CuO-NPs at doses of 250 and 500 mg/kg through oral gavage for 14 consecutive days. Multiple behavioral tests showed that CuO-NPs caused little changes in memory and learning performances as well as the locomotors activity, while the anxiety index increased. Copper NPs exposure increased also the liver and stomach relative weights and altered some blood biochemical parameters.

Aluminium oxide nanoparticles compromise spatial learning and memory performance in rats.

Recently, the biosafety and potential influences of nanoparticles on central nervous system have received more attention. In the present study, we assessed the effect of aluminium oxide nanoparticles (Al2O3-NPs) on spatial cognition. Male Wistar rats were intravenously administered Al2O3-NP suspension (20 mg/kg body weight/day) for four consecutive days, after which they were assessed. The results indicated that Al2O3-NPs impaired spatial learning and memory ability. An increment in malondialdehyde levels with a concomitant decrease in superoxide dismutase activity confirmed the induction of oxidative stress in the hippocampus. Additionally, our findings showed that exposure to Al2O3-NPs resulted in decreased acetylcholinesterase activity in the hippocampus. Furthermore, Al2O3-NPs enhanced aluminium (Al) accumulation and disrupted mineral element homoeostasis in the hippocampus. However, they did not change the morphology of the hippocampus. Our results show a connection among oxidative stress, disruption of mineral element homoeostasis, and Al accumulation in the hippocampus, which leads to spatial memory deficit in rats treated with Al2O3-NPs.

Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats: emotional behavior and pathophysiological examination.

Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.

Acute exposure to zinc oxide nanoparticles does not affect the cognitive capacity and neurotransmitters levels in adult rats.

With the industrialization and increasing public exposure, nano-sized materials have received much more concerns. However, the impact of zinc oxide nanoparticles (ZnO-NPs) on the human body, especially on the central nervous system is extremely limited. The aim of this study is to investigate the effects of ZnO-NPs on the behavioral performances and the brain contents of some monoamines neurotransmitters. Male Wistar rats were treated with a single intravenous injection of a suspension of ZnO-NPs (25 mg/kg body weight). Subsequently, 14 days after nanoparticles injection, the rats were sacrificed. During that period, Morris water maze and open-field tests were performed, respectively, for the spatial working memory and the analysis of locomotor activity of the rats. The data showed that plasma and brain zinc concentrations increased after administration of ZnO-NPs. However, brain content of neurotransmitters such as norepinephrine, epinephrine, dopamine and serotonin remained unchanged in ZnO-NPs-treated rats compared with control group. The results showed also that the working memory, locomotor activity and exploratory behavior were not impaired in ZnO-NPs exposed groups. These data revealed that acute intravenous injection of ZnO-NPs does not affect neurotransmitter contents, locomotor activity and spatial working memory in adult rats. Thus, the effect of nanoparticles on the behavioral performances is still a new topic that requires more attention.

Effect of TiO2 nanoparticles on emotional behavior and biochemical parameters in adult Wistar rats.

The rapidly developing field of nanotechnology is becoming a potential source for human exposure to nanoparticles. Titanium dioxide (TiO2) nanoparticles have been widely produced in industrial processes for several years. The aim of this study was to investigate the effects of TiO2 nanoparticles on plasmatic biochemical parameters and the emotional behavior in adult Wistar rats. Rats were treated by intraperitoneal injection of TiO2 nanoparticles (20-30 nm) at a dose of 25 mg/kg. For toxicity evaluation of nanoparticles sample, body weight, organ coefficient, blood biochemistry panel assay (AST, ALT, LDH, uric acid, creatinine, and glucose content) and emotional behavior parameters were determined. Sub-acute TiO2 nanoparticles treatment decreased the body weight, but increased the relative brain weight. Biochemical assessment in plasma samples showed that TiO2 nanoparticles injection increased uric acid concentration and AST activity in rats. However, the same treatment decreased the creatinine level, but had no effect on glucose concentration, ALT and LDH activity. The emotional behavior of control and treated rats was tested in elevated plus-maze. Interestingly, our results showed that TiO2-treated rats spent more time in the secured closed arms and entered the anxiogenic open arms less frequently than control. Our results suggest that TiO2 nanoparticles intoxication could altered biochemical parameters related to changes in organ function and leads to emotional behavior impairment of rats.

Chronic exposure to mercuric chloride during gestation affects sensorimotor development and later behaviour in rats.

The current study was performed to assess the effects of inorganic mercury (mercuric chloride - HgCl(2)) on the development of offsprings from intoxicated-mother during pregnancy. In this respect, pregnant rats were chronically treated with HgCl(2) at 50 ppm (Hg50) and 100 ppm (Hg100) in drinking water. After parturition, maternal behaviour was recorded during 30 min at 1st to 6th postnatal day (Pnd). The development of their offspring was studied during the first 17 days after birth. Sensorimotor development of pups was measured by different tests: rooting reflex, vibrissae placing response, righting reflex, negative geotaxis, suspension test and rotating grid. Two month after birth, the anxiety of offspring was tested using the elevated plus maze test. Our results indicate that mercury treatment significantly reduced the nursing and increased the time out the nest or drinking and eating. We also showed that prenatal exposure to HgCl(2) decreased weight gain. Importantly, the rooting reflex, the development of the vibrissae placing response, the righting reflex, the grip strength and the negative geotaxis behaviour were delayed in the offspring of dams treated with Hg50, the delay being more severe with Hg100. We also found a decrease in anxiety in adulthood. Cross-fostering test support the direct toxic effects of mercury.

Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate.

The aim of this study was to investigate the effects of FeSO(4) on the behavior of adult Wistar rats. Rats were treated with moderate doses of iron (1.5 or 3.0 mg/kg) for 5 consecutive days, and the effects of iron supplementation on emotional behavior were studied. One group of rats was tested in elevated plus-maze and in open field, and other group was tested for learning abilities in water maze and for motor skills in rotarod task. Iron level in the brain was measured in the frontal cortex, cerebellum, basal ganglia and hippocampus. The effects of the iron treatment (in particular, a dose of 3.0 mg/kg) on emotional behavior in the elevated plus maze and in the open field were significant. The effects of iron on spatial learning were less pronounced, but significant impairments due to the treatment were observed during the probe test. Motor skills and procedural learning in the rotarod task were not significantly affected by the treatment. These behavioral impairments were associated with significant iron accumulations in the hippocampus and basal ganglia of rats treated with 3.0 mg/kg iron and are discussed in terms of possible neuronal impairments of these structures. Thus, FeSO(4) administration at 3.0 mg/kg for 5 consecutive days in adult rats overcomes the mechanisms that shield the brain from iron intoxication and leads to behavioral impairments, in particular with respect to emotional behavior.

Free versus forced exposure to an elevated plus-maze: evidence for new behavioral interpretations during test and retest.

RATIONALE: The rodent elevated plus-maze is based on an approach/avoidance conflict between secure closed arms and aversive open arms that can be measured to assess anxiety. Despite this apparent simplicity, several discrepancies emerge from the interpretation of an animal's behavior in the maze, especially when considering the one-trial tolerance effect. OBJECTIVES AND METHODS: In order to bring new elements of interpretation, we compared the behavior of rats exposed to the standard version of the test (forced exposure) to the behavior of rats that were allowed to freely explore the apparatus. We also compared the effects of testing/retesting and chlordiazepoxide in these two situations. RESULTS: Our results confirm that open-arm avoidance is a natural tendency and therefore that it is not learned during initial exposure to the maze. In addition, comparison of the two situations suggests that some of the open-arm entries during a forced confrontation with the maze are better interpreted as attempts to avoid the whole situation, rather than as indications of a low level of anxiety. Finally, the one-trial tolerance effect was partially reduced in the free-exposure situation. CONCLUSIONS: Our results contradict the hypothesis that there is acquisition of a phobic-like response to open arms during trial 1. Rather, they are discussed in line with the hypotheses by Rodgers and Shepherd (Psychopharmacology (Berl) 113:237-242, 1993) and Bertoglio and Carobrez (Behav Brain Res 108:197-203, 2000) concerning the acquisition of spatial information about the whole apparatus, leading on trial 2 to an unbalanced approach/avoidance conflict and to the inefficiency of anxiolytic drugs.

Static magnetic field exposure affects behavior and learning in rats.

The present work investigated the behavioral effects of a moderate exposure (1 h per day for 5 consecutive days) to a static magnetic field (SMF, 128 mT) in male rats. SMF effects were evaluated in two sets of control and SMF-exposed rats. One set of animals was used for evaluation of SMF potential effects on emotional behaviors in the elevated plus maze and in the open field. The other set of animals was tested for learning and memory abilities in different procedures of the Morris water maze task. We found no significant difference between control and SMF-exposed rats in anxiety tests. However, the ratio of open arms time in the plus maze was reduced by half in SMF-exposed rats. In the Morris water maze, SMF-exposed rats were partially impaired during the initial learning task as well as in the retention task at one week. We conclude that static magnetic field exposure altered emotional behaviors in the plus maze and led to cognitive impairments, or at least to substantial attention disorders, in the Morris water maze.