Lead exposure induces autophagy via TLR4/EEF2 in neurons

Abstract

Chronic lead (Pb) exposure is known to cause neuronal inflammation and autophagy dysfunction. However, the precise mechanism by which Pb exposure triggers neuronal autophagy remains elusive. This study aimed to elucidate the molecular mechanisms underlying Pb-induced neuronal autophagy. Inflammation and autophagy are closely interconnected cellular processes, with Toll-like receptor 4 (TLR4) playing a significant role in the inflammatory response to Pb. We observed that inhibiting TLR4 resulted in increased expression of Eukaryotic elongation factor 2 (EEF2), which regulated cellular autophagy. The rats and HT22 cells were utilized to establish chronic Pb exposure models. Our data reveals that Pb exposure promotes neuronal autophagy, activates TLR4, and increases EEF2 expression in rat hippocampus and HT22 cells. Additionally, inhibiting TLR4 partially reverses the Pb-induced increase in autophagy and the enhanced expression of EEF2. Overexpression of EEF2 partially counteracted the autophagy induced by Pb exposure. These findings suggest that Pb-induced activation of TLR4 may upregulate EEF2 expression, thereby leading to augmented neuronal autophagy and potential neuronal dysfunction.