Prenatal restraint stress affects early neurobehavioral response and oxidative stress in mice pups.

Prenatal stress (PS), in both humans and animals, presents a potential risk to the mother and her fetus throughout gestation. PS is always associated with physiological changes that alter embryonic development and predispose the individual to lifelong health problems, including susceptibility to mental illness. This study aims to identify the harmful effects of prenatal restraint stress (PRS), commonly employed to induce stress painlessly and without any lasting debilitation during gestation. This stress is applied to pregnant Swiss albino mice from E7.5 to delivery for three hours daily. Our results show that PS affects dams' weight gain during the gestational period; moreover, the PS dams prefer passive nursing, exhibit a lower percentage of licking and grooming, and impair other maternal behaviors, including nesting and pup retrieval. Concerning the offspring, this stress induces neurobehavioral impairments, including a significant increase in the time of recovery of the young stressed pups in the surface righting reflex, the latency to avoid the cliff in the cliff avoidance test, longer latencies to accomplish the task in negative geotaxis, and a lower score in swimming development. These alterations were accompanied by increased Malondialdehyde activity (MDA) at PND17 and 21 and downregulation of AchE activity in the whole brain of pups on postnatal days 7 and 9. These findings demonstrated that PS causes deleterious neurodevelopmental impairments that can alter various behaviors later in life.

Corn oil and Soybean oil effect as vehicles on behavioral and oxidative stress profiles in developmentally exposed offspring mice.

Corn and soybean oils are among the most frequently used vehicles for water-insoluble compounds in toxicological studies. These two vegetable oils are nutrients and may induce some biological effects on animals that might interfere with the experimental results. However, their chronic effects on a developing brain have not been reported. This study aims to evaluate the neurobehavioral and brain biochemical effects of both oils on male and female Swiss albino mice. Pregnant female mice were exposed to 1 µl/g/d of either tap water, corn oil (CO), or soybean oil (SO) from early gestation (GD1) until weaning then offspring mice were exposed to the same treatment regimen until adulthood (PND70). Our results showed that developmental exposure to both oils induced body weight changes in offspring mice. In addition, we detected some behavioral abnormalities where both oil-treated groups showed a significant decrease in locomotor activity and greater levels of anxiety behavior. Moreover, our results suggest that continuous exposure to these oils may alter motor coordination, spatial memory and induce depression-like behavior in adult mice. These alterations were accompanied by increased malondialdehyde, superoxide dismutase, and glutathione peroxidase activities in specific brain regions. Together, these data suggest that exposure to CO and SO as vehicles in developmental studies may interfere with the behavioral response and brain redox homeostasis in offspring mice.

Impact of glyphosate-based herbicide exposure through maternal milk on offspring's antioxidant status, neurodevelopment, and behavior.

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH.

Sex-specific neurobehavioral and biochemical effects of developmental exposure to Malathion in offspring mice.

Malathion is an organophosphate pesticide (OP) commonly used in agriculture, industry, and veterinary medicine. Sex is a crucial factor in responding to neurotoxicants, yet the sex-specific effects of OP exposure, particularly neurological impairments following chronic low-level exposure remains limited. Our study aims to evaluate the neurobehavioral and biochemical effects of developmental exposure to Malathion across sexes. Pregnant mice were exposed to a low oral dose of Malathion from gestation up to the weaning of the pups, which were individually gavaged with a similar dose regimen until postnatal day 70. Our results show that Malathion decreased body weight and food intake, reduced locomotor activity and recognition memory. Motor coordination and special memory were only altered in females, whereas we found a male-specific effect of Malathion on social behavior and marble burying. These alterations were accompanied by increased malondialdehyde (MDA), decreased brain acetylcholinesterase activity (AChE), and disrupted brain redox homeostasis. Our findings about the effects of Malathion exposure across sexes may, in part, contribute to understanding the dimorphic susceptibilities observed in neurological disorders.

Gestational and Lactational Exposure to Malathion Affects Antioxidant Status and Neurobehavior in Mice Pups and Offspring.

Environmental factors such as pesticides are considered key determinants of brain damage and brain dysfunction. In the present work, we investigated the effect of an organophosphate pesticide, i.e., malathion, administrated peri- and postnatally on the antioxidant system as well as on acetylcholine esterase (AChE) activity in the brains of mice pups during the three postnatal weeks. Furthermore, we analyzed the behavior of the offspring just after weaning to assess the eventual effect of the pesticide on anxiety traits and social interaction. Concerning the biochemical biomarkers, the continuous treatment with malathion given either at a low dose of 5 mg/kg or at a medium one, 15 mg/kg, causes alterations in the activities of catalase, superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, accompanied by high level of peroxidation of membrane lipids, indicating a disturbance in intracellular redox homeostasis with subsequent increased intracellular oxidative stress. The effect was more pronounced when the high dose was applied. This was also demonstrated for the activity of AChE, downregulated at all postnatal ages investigated (5, 15, and 21), whereas the low dose (5 mg/kg) did not alter this enzymatic activity which is in line with the absence of locomotor activity alteration as assessed by open field (OF). With regard to this last test, results obtained show also that the treated offspring mice develop an anxiogenic state as evidenced by open field as well as an impairment of social interaction. Altogether, these results provide an accurate characterization of the association between neurobehavioral outcomes and brain alterations following malathion administrated in gestational and lactational periods, even given at low dose, classified as safe, and indicate clearly that the developing brain is sensitively vulnerable to this organophosphate pesticide.

Continuous Exposure to Inorganic Mercury Affects Neurobehavioral and Physiological Parameters in Mice.

Contamination with mercury is a real health issue for humans with physiological consequences. The main objective of the present study was to assess the neurotoxicological effect of inorganic mercury: HgCl2. For this, adult mice were exposed prenatally, postnatally, and during the adult period to a low level of the metal, and their behavior and antioxidant status were analyzed. First, we showed that mercury concentrations in brain tissue of treated animals showed significant bioaccumulation, which resulted in behavioral deficits in adult mice. Thus, the treated mice developed an anxiogenic state, as evidenced by open field and elevated plus maze tests. This anxiety-like behavior was accompanied by a decrease in social behavior. Furthermore, an impairment of memory in these treated mice was detected in the object recognition and Y-maze tests. The enzymatic activity of the antioxidant system was assessed in eight brain structures, including the cerebral cortex, olfactory bulb, hippocampus, hypothalamus, mesencephalon, pons, cerebellum, and medulla oblongata. The results show that chronic exposure to HgCl2 caused alterations in the activity of catalase, thioredoxin reductase, glutathione peroxidase, superoxide dismutase, and glutathione S-transferase, accompanied by peroxidation of membrane lipids, indicating a disturbance in intracellular redox homeostasis with subsequent increased intracellular oxidative stress. These changes in oxidative stress were concomitant with a redistribution of essential heavy metals, i.e., iron, copper, zinc, and magnesium, in the brain as a possible response to homeostatic dysfunction following chronic exposure. The alterations observed in overall oxidative stress could constitute the basis of the anxiety-like state and the neurocognitive disorders observed.