The effect of postnatal manganese exposure on the NMDA receptor signaling pathway in rat hippocampus

Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn²⁺ by intraperitoneal injection (n = 10/group: five males and five females). After 3 weeks of Mn exposure, messenger RNA (mRNA) and protein expression of NMDA receptor subunits (NR1, NR2A, and NR2B), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by real-time quantitative RT-PCR and Western blot. In Mn-exposed rats, decreased mRNA and protein expression of NR1, NR2A, and NR2B, CREB, and BDNF was observed. The results imply that downregulated NMDA receptor signaling pathway may be of vital importance in the neuropathological process of Mn-induced neurotoxicity.