Exposure to metam sodium-based pesticide impaired cognitive performances in adult mice: Involvement of oxidative damage and glial activation.

Cognitive integrity is a critical aspect of neurological function, and a decline in cognitive function is a hallmark of neurotoxicity. Oxidative stress is a significant pathological feature contributing to cognitive deficits that can arise from exposure to environmental pollutants such as pesticides. Among these, Metam sodium-based pesticides (MS-BP) are an emergent type of pesticide widely used in the agriculture and public health sectors for controlling pests and diseases. Our prior research has shown that animals exposed to MS-BP during the early stages of brain development caused cognitive impairments. In the present study, we tested whether exposure to this compound in a fully matured brain would affect cognitive performance and induce oxidative damage to the central nervous system. In this context, adult mice received chronic treatment with increasing doses of MS-BP and subjected to a set of behavioral paradigms. Following behavioral assessment, oxidative stress and glial activation were evaluated. Our main findings showed that MS-BP chronic exposure impaired recognition and short- and long-term memory. These alterations were accompanied by increased superoxide dismutase activity and malondialdehyde level and a marked decrease in catalase activity in specific brain areas. Moreover, exposure to MS-BP is associated with a significant rise in the density of astrocytic and microglial markers, indicating a possible glial cell response within the prefrontal cortex and hippocampus. The present work demonstrated that MS-BP altered cognitive performance likely through oxidative damage to the brain.

Chronic exposure to metam sodium-based pesticide in mice during adulthood elevated anxiety and depression-like behaviors: Involvement of serotoninergic depletion and gut microbiota dysbiosis.

Metam sodium-based pesticide (MS-BP) is widely used in agriculture and public health. We have previously demonstrated that maternal exposure to MS-BP resulted in sensorimotor alterations in mice offspring with long-lasting deficits including anxiety- and depression-like behaviors. Here, we project to verify whether these two neurobehavioral effects occur during adulthood following direct exposure to MS-BP and whether it results in changes in the serotoninergic system and gut microbiota. Our findings showed that chronic exposure to MS-BP increased anxiety- and depression-like behaviors, accompanied by a depletion of serotonin-like neurons within the dorsal raphe nucleus and a reduction in serotoninergic terminals in the infralimbic cortex and the basolateral amygdala. In addition, all MS-BP-exposed animals exhibited a reduced total bacterial number and diversity of gut microbiota. Taken together, our data demonstrated that MS-BP-induced behavioral changes could be related to the impairment of the serotoninergic system and gut microbiota dysbiosis.

Anxiety and Gene Expression Enhancement in Mice Exposed to Glyphosate-Based Herbicide.

Growing evidence demonstrates that serotonin (5-HT) depletion increases activity in the amygdala and medial prefrontal cortex (mPFC), ultimately leading to anxiety behavior. Previously, we showed that glyphosate-based herbicides (GBHs) increased anxiety levels and reduced the number of serotoninergic fibers within the mPFCs and amygdalas of exposed mice. However, the impact of this 5-HT depletion following GBH exposure on neuronal activity in these structures is still unknown. In this study, we investigated the effects of GBH on immediate early gene (IEG) activation within the mPFCs and amygdalas of treated mice from juvenile age to adulthood and its subsequent effects on anxiety levels. Mice were treated for subchronic (6 weeks) and chronic (12 weeks) periods with 250 or 500 mg/kg/day of GBH and subjected to behavioral testing using the open field and elevated plus maze paradigms. Then, we analyzed the expression levels of c-Fos and pCREB and established the molecular proxies of neuronal activation within the mPFC and the amygdala. Our data revealed that repeated exposure to GBH triggers anxiogenic behavior in exposed mice. Confocal microscopy investigations into the prelimbic/infralimbic regions of the mPFC and in basolateral/central nuclei of the amygdala disclosed that the behavioral alterations are paralleled by a robust increase in the density and labelling intensity of c-Fos- and pCREB-positive cells. Taken together, these data show that mice exposed to GBH display the hyperactivation of the mPFC-amygdala areas, suggesting that this is a potential mechanism underlying the anxiety-like phenotype.

Metam sodium exposure during pregnancy and lactation in mice caused behavioral abnormalities and oxidative stress in offspring.

Metam sodium (MS) is a widespread biocide with a broad-spectrum activity. Here, we addressed the behavioral impact of MS by exposing female mice to 50, 100 and 150 mg/kg of MS during both pregnancy and lactation, and evaluated the oxidative stress as a potential mechanism of MS-induced neurotoxicity. The results showed that MS affected fertility and reproduction parameters as well as some aspects of maternal behavior, especially at high doses. In offspring, MS caused a significant delay in the ontogeny of sensorimotor functions. In addition, treated mice exhibited during adulthood an increase of anxiety-like, depression-like behaviors as well as learning and memory impairment. These alterations were accompanied by an increase of the superoxide dismutase activity, and a significant decreased catalase and malondialdehyde activities in specific brain areas. The present work revealed that early exposure to MS induced sensorimotor and behavioral impairments in offspring likely associated with onset of oxidative stress.

Prenatal exposure to the pesticide metam sodium induces sensorimotor and neurobehavioral abnormalities in mice offspring.

The present study has investigated developmental neurotoxicity of Metam sodium (MS), from gestational day 6 and throughout the gestation period until delivery. Therefore, mated female mice were orally exposed on a daily basis to 0 (control), 50, 100 or 150 mg of MS/kg of body weight and their standard fertility and reproductive parameters were assessed. The offspring were examined for their sensorimotor development, depression and cognitive performance. Our results showed that MS exposure during pregnancy led to one case of mortality, two cases of abortion and disturbed fertility and reproductive parameters in pregnant dams. In offspring, MS induced an overall delay in innate reflexes and sensorimotor performances. Furthermore, all prenatally treated animals showed an increased level of depression-like behavior as well as a pronounced cognitive impairment in adulthood. These results demonstrated that prenatal exposure to MS causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice.

Learning and memory impairments associated to acetylcholinesterase inhibition and oxidative stress following glyphosate based-herbicide exposure in mice.

Numerous clinical and epidemiological data have reported the deleterious effects of glyphosate on learning and memory. The ability of this herbicide to cross the blood-brain barrier may have adverse effects on the structure and various functions of the nervous system. This study was conducted to highlight the effects of Glyphosate-based herbicide (GBH) on these two functions in mice treated daily with 250 or 500 mg/kg following acute (unique administration), subchronic (6 weeks) and chronic (12 weeks) treatments. The integrity of learning and memory was assessed by using a specific behavioral test battery: Novel object recognition, Y-maze and passive avoidance tasks. The acetylcholinesterase (AChE) and anti-oxidant enzyme activities, especially superoxide dismutase (SOD) and peroxidase (PO) were evaluated. Our results indicated that unlike acute treatment, both subchronic and chronic exposure to GBH decreased discrimination index and the step-through-latency indicating recognition and retention memory impairments, respectively. In contrast, only chronic exposure affected working memory manifested by decreased spontaneous alternation. Furthermore, our results showed also a prominent decrease in AChE, SOD and PO specific activities within the brain of treated mice following repeated exposures. This study demonstrates that GBH induced numerous cognitive abnormalities referred to different forms of memory likely associated with a significant inhibition of AChE activity and oxidative stress induction.