Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice

Abstract

Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH) exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks) and chronic (12 weeks) exposure (250 or 500 mg/kg/day) in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF), the elevated plus maze, the tail suspension and Splash tests (STs). Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and serotonin (5-HT) in the dorsal raphe nucleus (DRN), the basolateral amygdala (BLA) and the ventral medial prefrontal cortex (mPFC) was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes.

Glyphosate and glyphosate‐based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome

“…It is likely, however, that separation causes some form of anxiety not only for the pup, but also for the mother. Interestingly, previous work suggests that early or adult exposure to Glyphosate‐based herbicide increases anxiety and depression‐like behaviour in rodents . Therefore, we can speculate that the altered interpretation of the social environment associated with anxiety or depressive‐like behaviour will result in modification in maternal care.…”

“…For example, high doses of Glyphosate lead to an increase in serotonin release and turnover in the striatum and hypothalamus and in dopamine turnover in prefrontal cortex and hippocampus . The change in dopamine is likely to be related to the reduction of tyrosine hydroxylase expression, the key enzyme responsible for dopamine synthesis. The modulation of dopamine levels can also be associated with a reduction in D1‐dopamine specific receptor binding in the nucleus accumbens of adult male Sprague‐Dawley rats exposed to Glyphosate .…”

“…Indeed, GBH induced alteration in neurotransmitter dopamine, norepinephrine, serotonin and glutamate levels and their metabolites in several brain regions, such as the hippocampus, substantia nigra and prefrontal cortex in adult male rats, as well as neurotransmitter binding to their cognate receptor . Consequently, these alterations in neurotransmission are likely to be the cause of deficits in locomotor activity and depressive‐ and anxiety‐like symptoms observed in male mice and male and female rats following glyphosate exposure . Interestingly, although several studies have investigated the effect of perinatal exposure to GBH via the exposure to gestating and lactating females, there is no information about the mother's behaviour and brain plasticity and how the dam herself could be affected by the treatment.…”

“…is known to be associated with significant alterations of the organism's physiology, including defect in brain neurodevelopment and neuroplasticity . Recently, a few studies showed that GBH exposure can affect gut microbiota, a process known as dysbiosis and that such an alteration could result in mental health disorders, including anxiety and depression . Alternatively, or in addition, glyphosate possess chelating properties and binds divalent cations (e.g.…”

Pesticides used in Europe and autism spectrum disorder risk: can novel exposure hypotheses be formulated beyond organophosphates, organochlorines, pyrethroids and carbamates? - A systematic review

“…Social interaction was evaluated by observing aggressive behaviors in the resident-intruder test (Sano et al, 2016). Restricted interests were assessed using the open field test (OFT) (Ait Bali et al, 2018;Ait Bali et al, 2017;Khalil et al, 2017;Cattani et al, 2017;Gallegos et al, 2016;Godinho et al, 2016;Moser et al, 2001). This test consists in placing mice in a large and brightly light box.…”