Abstract：
Carnosine is a naturally occurring endogenous dipeptide with well-recognized anti-inflammatory, antioxidant, and neuroprotective effects at the central nervous system level. To date, very few studies have been focused on the ability of carnosine to rescue and/or enhance memory. Here, we used a well-known invertebrate model system, the pond snail Lymnaea stagnalis, and a well-studied associative learning procedure, operant conditioning of aerial respiration, to investigate the ability of carnosine to enhance long-term memory (LTM) formation and reverse memory obstruction caused by an immune challenge (i.e., lipopolysaccharide [LPS] injection). Exposing snails to 1 mM carnosine for 1 h before training in addition to enhancing memory formation resulted in a significant upregulation of the expression levels of key neuroplasticity genes (i.e., glutamate ionotropic receptor N-methyl-d-aspartate [NMDA]-type subunit 1-LymGRIN1, and the transcription factor cAMP-response element-binding protein 1-LymCREB1) in snails\' central ring ganglia. Moreover, pre-exposure to 1 mM carnosine before an LPS injection reversed the memory deficit brought about by inflammation, by preventing the upregulation of key targets for immune and stress response (i.e., Toll-like receptor 4-LymTLR4, molluscan defense molecule-LymMDM, heat shock protein 70-LymHSP70). Our data are thus consistent with the hypothesis that carnosine can have positive benefits on cognitive ability and be able to reverse memory aversive states induced by neuroinflammation.
摘要：
肌肽是一种天然存在的内源性二肽，具有公认的抗炎作用，抗氧化剂，和中枢神经系统水平的神经保护作用。迄今为止,很少有研究关注肌肽挽救和/或增强记忆的能力。这里,我们使用了一个著名的无脊椎动物模型系统，池塘蜗牛Lymnaeastagnalis，和一个经过充分研究的联想学习程序，空中呼吸的操作性调节，调查肌肽增强免疫攻击引起的长期记忆(LTM)形成和反向记忆障碍的能力(即，脂多糖[LPS]注射液）。在训练前将蜗牛暴露于1mM肌肽1小时，除了增强记忆形成外，还导致关键神经可塑性基因的表达水平显着上调（即，谷氨酸离子型受体N-甲基-d-天冬氨酸[NMDA]型亚基1-LymGRIN1和转录因子cAMP反应元件结合蛋白1-LymCREB1）在蜗牛中。此外，在LPS注射前预先暴露于1mM肌肽逆转了炎症带来的记忆缺陷，通过防止免疫和应激反应的关键靶标上调(即，Toll样受体4-LymTLR4，软体动物防御分子-LymMDM，热休克蛋白70-LymHSP70)。因此，我们的数据与以下假设一致：肌肽可以对认知能力产生积极的益处，并且能够逆转由神经炎症引起的记忆厌恶状态。
