Glyphosate and Glutamate Neuroexcitotoxicity
Cattani et al. have demonstrated that maternal exposure of pregnant rats to glyphosate-based herbicide leads to glutamate neuroexcitotoxicity in the hippocampus of the offspring [78]. Exposure of pregnant female Wistar rats to the glyphosate-based herbicide Roundup at the no observed adverse effect level (NOAEL) for maternal toxicity, during pregnancy and lactation, led to significant neuroexcitotoxicity effects in the brains of the pups, due to excess extracellular glutamate [78]. Roundup reduced glutamate uptake from the synapse by astrocytes and increased the release of glutamate into the synaptic cleft by neurons in the hippocampus. Glyphosate suppressed the enzyme glutamine synthetase in astrocytes, impairing their ability to safely store glutamate as glutamine. Glyphosate also reduced the levels of glutathione and increased the levels of lipid peroxidation products [78]. Excess extracellular glutamate disrupts cystine (a cysteine dimer) uptake by cells via the Cystine/Glutamate Antiporter System xc-. This depletes the levels of glutathione, since cysteine is the rate-limiting substrate for glutathione synthesis [79].
In another study by Cattani et al., rats chronically exposed to low-dose glyphosate both prenatally and postnatally exhibited evidence of glutamate-related neurotoxicity at 60 days of age [80]. The exposed rats exhibited oxidative stress markers associated with depressive-like behavior. Astrocyte activation was suggested by elevated serum levels of the astrocytic protein S100B, a marker of astrocyte activation. S100B serum levels have been found to be elevated in association with autism [81]. A study on 40 patients suffering from poisoning by either glyphosate (23) or glufosinate [82] (17) found statistically significant correlations between serum levels of S100B and neurological complications [83].
Glyphosate exposure to goldfish (as Roundup) at low levels induced oxidative stress and suppressed the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase, and glucose-6-phosphate dehydrogenase in the tissues of the fish. SOD activities were reduced by 51 to 68% in the brain [84]. All these enzymes play important roles in reducing oxidative stress.
A comprehensive review paper with over 200 references detailed the toxic effects of glyphosate specifically on the nervous system. These authors wrote: “The results analyzed herein reflect the capacity of glyphosate to induce oxidative stress, neuroinflammation, and mitochondrial dysfunction, processes that lead to neuronal death by autophagia, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders.” [85], p. 27.