Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat

Abstract

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague–Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12–14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.

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Funding

This work was supported by Grants CONACYT #251510 and UNAM-DGAPA- PAPIIT Grant # IN 203916 to VMR. D. Y. Reyes-Bravo received a fellowship (628655) from CONACYT; M. E. Chávez-Pichardo and K. Domínguez-Marchan received a fellowship from UNAM-DGAPA-PAPIIT Grant IN203916.

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Chávez-Pichardo, M.E., Reyes-Bravo, D.Y., Mendoza-Trejo, M.S. et al. Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat. Arch Toxicol (2020). https://doi.org/10.1007/s00204-020-02806-2

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Keywords

  • Herbicides
  • Neurotoxicity
  • GABA
  • Glutamate
  • Locomotor activity
  • Behavior