The effect of nuclear factor erythroid 2-related factor/antioxidant response element signalling pathway in the...

Lanthanum exerts adverse effects on the central nervous system. However, the mechanism underlying these adverse effects has not been clarified. It is known that oxidative stress plays an important role in neurological injuries induced by harmful factors. Nuclear factor erythroid 2-related factor (Nrf2) is very important in the response to oxidative stress in tissues and cells. The purpose of this study was to explore the effect of lanthanum chloride (LaCl₃ ) on the spatial learning and memory of rats and to determine whether the Nrf2/antioxidant response element pathway acts in the hippocampus. Four groups of Wistar rats were exposed to 0 mM, 9 mM, 18 mM or 36 mM LaCl₃ through their drinking water from the day of birth to 2 months after weaning. The results showed that LaCl₃ impaired the spatial learning and memory of the rats, damaged the neuronal ultrastructure, increased reactive oxygen species levels and significantly down-regulated Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1, haeme oxygenase-1, superoxide dismutase 2, glutathione peroxidase 1, glutathione-S-transferase, γ-glutamine cysteine synthase and glutathione reductase, in the hippocampus. This study suggests that LaCl₃ can impair the spatial learning and memory of rats, possibly by perturbing the Nrf2/antioxidant response element signalling pathway.