Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress

Abstract

We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats. The subchronic exposure to the pesticide decreased L-[C]-glutamate uptake and increased Ca influx in 60-day-old rat hippocampus, suggesting a persistent glutamate excitotoxicity from developmental period (PND15) to adulthood (PND60). Moreover, GBH exposure alters the serum levels of the astrocytic protein S100B. The effects of GBH exposure were associated with oxidative stress and depressive-like behavior in offspring on PND60, as demonstrated by the prolonged immobility time and decreased time of climbing observed in forced swimming test. The mechanisms underlying the GBH-induced neurotoxicity involve the NMDA receptor activation, impairment of cholinergic transmission, astrocyte dysfunction, ERK1/2 overactivation, decreased p65 NF-κB phosphorylation, which are associated with oxidative stress and glutamate excitotoxicity. These neurochemical events may contribute, at least in part, to the depressive-like behavior observed in adult offspring.

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

“…These substances included glyphosate,23242526 chlorpyrifos,927 diazinon,282930 acephate,313233 malathion,333435 permethrin,69 bifenthrin,93336 methyl bromide,3738 imidacloprid,3940 avermectin,4142 and myclobutanil 1443…”

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

“…It should be noted that the nucleus accumbens is a fundamental brain region involved in the motivation aspect of maternal behaviour and modulation of activity within this brain region only can alter proper maternal care toward the offspring . In addition to monoamines, acetylcholine esterase, which is the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft to terminate synaptic transmission, is inhibited in the prefrontal cortex, striatum and hippocampus of male and female adult offspring after a perinatal exposure to Glyphosate . The extracellular glutamate concentration and the reuptake of amino acids are also hindered in the hippocampus following exposure to Glyphosate‐based herbicide …”

“…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.…”

“…It should be added that the ventral and dorsal region of the hippocampus present physiological and functional differences, with the agreed consensus that the dorsal hippocampus is involved in spatial cognition and more cognitive performance and memory in general, whereas the ventral part is involved in the regulation of emotions, including stress and anxiety . Previous data suggest the GBH exposure affects hippocampal physiology and plasticity . To our knowledge, there are no data available on how glyphosate could affect maternal behaviour and the associated neuroplasticity.…”

“…Although it is hypothesised that the effects of glyphosate in the brain might be linked to glutamate excitotoxicity and oxidative stress, the molecular target(s) of glyphosate in the brain is/are not well defined. As introduced above, glyphosate is best known for its direct inhibitory effects on EPSPS.…”