Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, 52621 Tel HaShomer, Israel.
Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Neural Plast. 2021 Jan 13;2021:8813734. doi: 10.1155/2021/8813734. eCollection 2021.
The cholinergic system plays a fundamental role in learning and memory. Pharmacological activation of the muscarinic receptor M1R potentiates NMDA receptor activity and induces short-term potentiation at the synapses called muscarinic LTP, mLTP. Dysfunction of cholinergic transmission has been detected in the settings of cognitive impairment and dementia. Systemic inflammation as well as neuroinflammation has been shown to profoundly alter synaptic transmission and LTP. Indeed, intervention which is aimed at reducing neuroinflammatory changes in the brain has been associated with an improvement in cognitive functions. While cognitive impairment caused either by cholinergic dysfunction and/or by systemic inflammation suggests a possible connection between the two, so far whether systemic inflammation affects mLTP has not been extensively studied. In the present work, we explored whether an acute versus persistent systemic inflammation induced by LPS injections would differently affect the ability of hippocampal synapses to undergo mLTP. Interestingly, while a short exposure to LPS resulted in a transient deficit in mLTP expression, a longer exposure persistently impaired mLTP. We believe that these findings may be involved in cognitive dysfunctions following sepsis and possibly neuroinflammatory processes.
胆碱能系统在学习和记忆中起着至关重要的作用。毒蕈碱受体 M1R 的药理学激活增强了 NMDA 受体的活性，并在称为毒蕈碱长时程增强（mLTP）的突触处诱导短期增强。在认知障碍和痴呆的情况下，已经检测到胆碱能传递功能障碍。系统性炎症以及神经炎症已被证明会深刻改变突触传递和长时程增强。事实上，旨在减少大脑中神经炎症变化的干预措施与认知功能的改善相关。虽然由胆碱能功能障碍和/或系统性炎症引起的认知障碍表明两者之间可能存在联系，但到目前为止，系统性炎症是否会影响 mLTP 尚未得到广泛研究。在本工作中，我们探讨了 LPS 注射引起的急性与持续性系统性炎症是否会以不同的方式影响海马突触发生 mLTP 的能力。有趣的是，虽然 LPS 的短暂暴露导致 mLTP 表达的短暂缺陷，但较长时间的暴露会持续损害 mLTP。我们认为这些发现可能与败血症后的认知功能障碍以及可能的神经炎症过程有关。
