Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Instituto Latino-Americano de Ciências da Vida e Saúde, Universidade Federal da Integração Latino-Americana (UNILA), Brazil.
Neurobiol Learn Mem. 2021 Apr;180:107422. doi: 10.1016/j.nlm.2021.107422. Epub 2021 Mar 7.
N-methyl D-aspartate (NMDA) administered at subtoxic dose plays a protective role against neuronal excitotoxicity, a mechanism described as preconditioning. Since the activation of adenosinergic receptors influences the achievement of NMDA preconditioning in the hippocampus, we evaluated the potential functional interplay between adenosine A and A receptors (AR and AR) activities and NMDA preconditioning. Adult male Swiss mice received saline (NaCl 0.9 g%, i.p.) or a nonconvulsant dose of NMDA (75 mg/kg, i.p.) and 24 h later they were treated with the one of the ligands: AR agonist (CCPA, 0.2 mg/kg, i.p.) or antagonist (DPCPX, 3 mg/kg, i.p.), AR agonist (CGS21680, 0.05 mg/kg, i.p.) or antagonist (ZM241385, 0.1 mg/kg, i.p.) and subjected to contextual fear conditioning task. Binding properties and content of AR and glutamate uptake were assessed in the hippocampus of mice subjected to NMDA preconditioning. Treatment with CGS21680 increased the time of freezing during the exposure of animals to the new environment. NMDA preconditioning did not affect the freezing time of mice per se, but it prevented the response observed after the activation of AR. Furthermore, the activation of AR by CGS21680 after the preconditioning blocked the increase of glutamate uptake induced by NMDA preconditioning. The immunodetection of AR in total hippocampal homogenates showed no significant differences evoked by NMDA preconditioning and did not alter AR maximum binding for the selective ligand [H]CGS21680. These results demonstrate changes in AR functionality in mice following NMDA preconditioning.
N-甲基-D-天冬氨酸（NMDA）在亚毒性剂量下发挥神经保护作用，这种机制被描述为预处理。由于腺苷能受体的激活影响了海马中 NMDA 预处理的实现，我们评估了腺苷 A 和 A 受体（AR 和 AR）活性与 NMDA 预处理之间的潜在功能相互作用。成年雄性瑞士小鼠接受生理盐水（NaCl 0.9%，腹腔内注射）或非惊厥剂量的 NMDA（75mg/kg，腹腔内注射），24 小时后，它们接受以下一种配体的治疗：AR 激动剂（CCPA，0.2mg/kg，腹腔内注射）或拮抗剂（DPCPX，3mg/kg，腹腔内注射），AR 激动剂（CGS21680，0.05mg/kg，腹腔内注射）或拮抗剂（ZM241385，0.1mg/kg，腹腔内注射），并进行情境恐惧条件反射任务。在接受 NMDA 预处理的小鼠的海马中评估了 AR 和谷氨酸摄取的结合特性和含量。用 CGS21680 处理增加了动物暴露于新环境时的冻结时间。NMDA 预处理本身不会影响小鼠的冻结时间，但它阻止了 AR 激活后观察到的反应。此外，CGS21680 激活 AR 后，阻断了 NMDA 预处理诱导的谷氨酸摄取增加。用 NMDA 预处理引起的总海马匀浆中 AR 的免疫检测没有显示出显著差异，也没有改变 AR 对选择性配体 [H]CGS21680 的最大结合。这些结果表明 NMDA 预处理后，小鼠 AR 的功能发生了变化。
