Neurotoxicity induced by the pyrethroid lambda-cyhalothrin: Alterations in monoaminergic systems and dopaminergic and serotoninergic pathways in the rat brain.

ABSTRACT

The effects of Type II pyrethroid lambda-cyhalothrin on dopamine (DA) and serotonin (5-HT) synthesis in rat brain regions (striatum, hippocampus, prefrontal cortex, hypothalamus and midbrain) were studied. Lambda-cyhalothrin (1, 4 and 8 mg/kg bw, oral gavage, 6 days) induced a decrease of DA, 5-HT and metabolites contents, in a brain regional- and dose-related manner. The major decreases in DA and 5-HT contents were observed in hippocampus and prefrontal cortex tissues. This research study also showed in hippocampus and prefrontal cortex, that lambda-cyhalothrin modified the mRNA levels of DA transporter gene (Dat1 up-regulation), 5-HT transporter gene (SERT down-regulation), DA receptor genes (Drd1and Drd2 down-regulation), 5-HT receptor genes (5-HT1A and 5-HT2A down-regulation/up-regulation), DA synthesis gene (TH down-regulation), 5-HT synthesis gene (TPH2 down-regulation), DA and 5-HT degradation genes (MAOA and MAOB up-regulation). These results reveal that lambda-cyhalothrin altered central nervous system (CNS) monoaminergic neurotransmitters. Lambda-cyhalothrin evoked a selective neurotoxic injury to dopaminergic and serotoninergic pathways. These findings may clarify on the pyrethroids-induced neurotoxicity mechanisms and could involve pyrethroids as environmental risk factors leading to the development of neurodegenerative diseases.