Lanthanum chloride impairs memory in rats by disturbing the glutamate-glutamine cycle and over-activating NMDA receptors

Food Chem Toxicol. 2018 Mar:113:1-13. doi: 10.1016/j.fct.2018.01.023. Epub 2018 Jan 17.

Abstract

Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain barrier, accumulate in the brain and affect the spatial learning and memory abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter, and the excessive Glu accumulation in extracellular space can induce excitatory neurotoxicity. This study was designed to research the influence of LaCl3 on the spatial learning and memory abilities of rats and to discuss the possible mechanism underlying this effect regarding the extracellular Glu concentration, the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors. Four groups of Wistar rats were exposed to 0%, 0.125%, 0.25% or 0.5% LaCl3 via the drinking water from the day of conception to 1 month after weaning. These results showed that LaCl3 exposure damaged spatial learning and memory, long-term potentiation, and neuronal ultrastructure, generated an excessive accumulation of glutamate, significantly decreased the expression of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), glutamine synthetase (GS) and phosphate-activated glutaminase (PAG), and increased the expression of GluN1, GluN2A and GluN2B. This study showed that LaCl3 impaired the rats' spatial learning and memory abilities by disturbing the Glu-Gln cycle and over-activating NMDA receptors thereby inducing excitotoxicity.

Keywords: Glutamate; Hippocampus; Lanthanum; Learning and memory; NMDA receptors.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Female
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamic Acid / metabolism*
  • Glutaminase / metabolism
  • Glutamine / metabolism*
  • Lanthanum / pharmacology*
  • Long-Term Potentiation / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Microscopy, Electron, Transmission
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Spatial Learning / drug effects

Substances

  • Excitatory Amino Acid Transporter 1
  • Receptors, N-Methyl-D-Aspartate
  • lanthanum chloride
  • Glutamine
  • Glutamic Acid
  • Lanthanum
  • Glutaminase
  • Glutamate-Ammonia Ligase