The protective function of taurine on pesticide‐induced permanent neurodevelopmental toxicity in juvenile rats

Abstract

Numerous studies have confirmed that prenatal or early postnatal exposure to pesticides can lead to functional deficits in the developing brain. This study aimed to investigate whether combined exposure to paraquat (PQ) and maneb (MB) during puberty could cause permanent toxic effects in the neural system of rats. In addition, the neuroprotective function of taurine (T) and its possible mechanism were investigated. Rats were administered PQ + MB intragastrically for 12 continuous weeks, while taurine dissolved in water was fed to the rats for 24 continuous weeks. In the behavioral tests, the rats' trajectories became complex, and the reaction latencies and mistake frequencies increased. Significant changes were found in the hippocampal neurons of the PQ + MB groups but not in the taurine treatment groups. PQ + MB stimulated cAMP to reduce the production of protein kinase A (PKA) and inhibited the activation of other elements, such as brain‐derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), phospho‐CREB (p‐CREB), immediate‐early genes (IEGs)Arc, and c‐Fos. Importantly, taurine regulated the level of cAMP and the expression of the abovementioned proteins. Together, our findings implied that adolescent exposure to PQ + MB may impact the behavior and cognitive function of rats via the cAMP‐PKA‐CREB signaling pathway, while taurine may in turn exert neuroprotection by diminishing these impacts.

Time for Re-Evaluating the Human Carcinogenicity of Ethylenedithiocarbamate Fungicides? A Systematic Review

“…In rats treated orally with Mancozeb, dose-related signs of neurotoxicity were also noticed, including adynamia, muscular tone reduction, loss of motor coordination, paralysis of the lower limbs, loss of appetite, and prostration [ 16 , 17 ]. Adverse neurodevelopmental effects were also observed in rats fed with Maneb and Paraquat during puberty, which were prevented by adding taurine to the diet [ 96 ]. In vitro studies have shown that Zineb is capable of inducing apoptosis in SH-SY5Y human neuroblastoma cells, suggesting that the same effect would occur in dopaminergic neurons [ 97 ].…”

Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity

“…Combined exposure to paraquat and maneb reduced PKA production through cAMP stimulation and, thus, inhibited activating elements like BDNF, CREB, ARC, C-JUN, C-FOS, etc. [ 48 , 49 ]. Further, BDNF downregulation eventually reduces the Creb mRNA and protein levels through the MER/ERK pathway [ 50 ].…”