Regulatory role of GLUT1 in lead-induced neurotoxicity and the neuroprotective effect of Morinda officinalis oligosaccharides.

Lead (Pb) is a neurotoxic environmental pollutant that causes cognitive dysfunction and metabolic disturbances in the brain. Glucose transporter 1 (GLUT1) is essential for cerebral glucose metabolism, and altered expression may impair glucose uptake and utilization, synaptic plasticity, and cognitive performance. We found that acute Pb exposure impaired learning, memory, and anxiety-related behavior of mice. Fasting blood glucose concentrations increased in Pb-exposed mice, whereas GLUT1 expression in the brain was significantly decreased. GLUT1 overexpression alleviated Pb-induced synaptic structural and functional damage in Neuro-2a cells, whereas GLUT1 knockdown exacerbated these effects. Co-treatment with Morinda officinalis oligosaccharides (MOOs) improved behavioral performance, restored GLUT1 expression, and reduced Pb-induced synaptic pathology, whereas BAY-876 aggravated neurological impairment. In conclusion, GLUT1 is a key regulator of Pb-induced neurotoxicity. These findings provide potential therapeutic strategies for preventing the neurotoxic effects of Pb.