AMPA受体
谷氨酸受体
海马体
敌手
内分泌学
谷氨酸的
神经毒性
内科学
医学
生物
神经科学
受体
毒性
作者
José Afonso Corrêa Silva,Lariza Oliveira de Souza,Maria Paula Arakaki Severo,Sarah Luize Camargo Rodrigues,Patrícia Molz,Patrícia Schönhofen,Alice Laschuk Herlinger,Nadja Schröder
出处
期刊:Research Square - Research Square
日期:2024-01-12
标识
DOI:10.21203/rs.3.rs-3809589/v1
摘要
Abstract Iron accumulation has been associated with the pathogenesis of neurodegenerative diseases and memory decline. As previously described by our research group, iron overload in the neonatal period induces persistent memory deficits, increases oxidative stress, and apoptotic markers. The neuronal insult caused by iron excess generates an energetic imbalance that can alter glutamate concentrations and thus trigger excitotoxicity. Drugs that block glutamatergic receptor, eligibly mitigate neurotoxicity; among them, Perampanel (PER), a reversible AMPA receptor (AMPAR) antagonist. In the present study, we sought to investigate the neuroprotective effects of PER in rats subjected to iron overload in the neonatal period. Recognition and aversive memory were evaluated, AMPAR subunit phosphorylation, as well as the relative expression of genes such as GRIA1, GRIA2, DGL4 , and CAC , which code proteins involved in AMPAR anchoring. Male rats received vehicle or carbonyl iron (30 mg/kg) from the 12th to the 14th postnatal day and were treated with vehicle or PER (2 mg/kg) for 21 days in adulthood. The excess of iron caused recognition memory deficits and impaired emotional memory, and PER was able to improve the rodents' memory. Furthermore, iron overload increased the expression of the GRIA1 gene and decreased the expression of the DGL4 gene, demonstrating the influence of metal accumulation on the metabolism of AMPAR. These results suggest that iron can trigger changes in the expression of genes important for the assembly and anchoring of AMPAR and that blocking AMPAR with PER is capable of partially reversing the cognitive deficits caused by iron overload.
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