EVALUATION OF MITOCHONDRIAL AND NEUROBEHAVIORAL DISORDERS IN BRAIN REGIONS OF OFFSPRING (F1, F2) AFTER GESTATING AND LACTATING FEMALE RATS EXPOSURE TO LOW-DOSE OF IMIDACLOPRID AND CYPERMETHRIN

Abstract

The imidacloprid (IMID) and cypermethrin (CYP) pesticides are known to have neurotoxic effects and negative brain developmental consequences when used separately, but little is known about the consequences of using them as a mixture. That could be passed down from one generation to the next. In this context, we were interested in studying the effect of oral exposure of female rats during gestation and throughout the lactational period to real doses of IMID (1.2 mg/kg) and CYP (6.7 mg/kg) either alone or in a mixture on behavior and mitochondrial redox status. The first and second generation pups were followed from birth to juvenile age using a series of tests to assess reflex, coordination and general motor function, including surface righting, cliff aversion, negative geotaxis and the muscle strength test. At PND 21, cholinergic function, oxidative stress and mitochondrial integrity were assessed in the striatum and hippocampus. Our results showed that IMID and CYP, alone or in combination, induced decreased body weight gain, impaired neurobehavioral performance, and AchE inhibition. Oxidative stress markers including GSH level and SOD, CAT, GST and GPx activities showed a significant decrease. While, lipid peroxidation which was assessed by MDA assay, cytosolic calcium level, swelling and mitochondrial permeability recorded a significant increase. In conclusion, the disruption of mitochondrial redox homeostasis and the presence of neurobehavioral disorders even in the offspring of the F2 generation suggests that independent and combined exposure to IMID and CYP during a critical period of development has irreversible effects; long-lasting and persistent.