Neurotoxicity of ammonium glufosinate and its formulations during development: in vivo and in vitro evidence.

The increasing use of ammonium glufosinate (GLA), following the emergence of weeds resistant to other herbicides, has heightened the scientific community’s interest in its toxic effects on non-target organisms. The nervous system is of particular interest due to its strong structural similarity to glutamate, an excitatory neurotransmitter. Moreover, GLA is an irreversible inhibitor of glutamine synthetase; which could therefore cause structural and functional neurotoxicity. Thus, our study aims to evaluate the neurotoxicity induced by GLA on the CNS through in vivo and in vitro approaches. Wistar rats were exposed to a commercial formulation of GLA at doses of 20 and 40 mg/kg bw from postnatal day 7 to 27. Several behavioral tests were conducted to assess motor activity and cognitive functioning such as: the Open Field Test, Object Recognition Memory Test, and Rotarod Test. Results showed delayed growth in those exposed to the highest doses of the herbicide as well as decreased learning, and memory alterations. Additionally, hippocampal neurons, exposed to pure GLA and a commercial formulation for 48 hr, revealed marked effects on dendrite development since a reduced complexity of dendritic tree was observed by confocal microscopy. Preliminary analyses also showed a decrease in the level of proteins associated with synaptic function. Additionally, GLA treatment induced a downregulation of CaMKII/JNK pathways, which are involved in neuronal development and plasticity process.