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.