Lanthanum damages learning and memory and suppresses astrocyte-neuron lactate shuttle in rat hippocampus

Abstract

Rare-earth elements (REEs) are applied in various fields by virtue of their superior physical and chemical properties. Surveys have reported that REEs can impair learning and memory in children and induce neurobehavioral abnormalities in animals. However, the mechanism underlying this neurotoxicity is still unclear. Lanthanum (La) is often chosen to study the effects of REEs. Here, we investigated the role of astrocyte-neuron lactate shuttle (ANLS) in spatial learning and memory impairment induced by LaCl₃ in hippocampus, an important spatial memory-related brain region. Pregnant Wistar rats were exposed to 0, 0.125, 0.25, 0.5, or 1% LaCl₃ in drinking water during pregnancy and lactation. After weaning, young rats continued to receive 0, 0.125, 0.25, 0.5, and 1% LaCl₃ in the drinking water for 1 month. The results showed that LaCl₃ exposure impaired the spatial learning and memory of rats in Morris water maze test, significantly reduced the mRNA and protein levels of glycogen synthetase, glycogen phosphorylase, lactate dehydrogenase A, monocarboxylate transporter 4, MCT-1, and MCT-2, and decreased total LDH activity and lactate contents in rat hippocampus. These results indicate that LaCl₃ impairs spatial learning and memory in rats probably by suppressing ANLS in rat hippocampus. The study provides a novel clue of energy supply for neurons to clarify the neurotoxicity of REEs.

Keywords: Astrocyte–neuron lactate shuttle (ANLS); Hippocampus; Lanthanum; Learning and memory.