Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.
Eur J Neurosci. 2023 Nov;58(10):4123-4136. doi: 10.1111/ejn.16165. Epub 2023 Oct 23.
It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signalling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability, cause neuronal structure disorder and influence gamma oscillations. These might be mediated by the inhibition of prostaglandin (PG) E2/cAMP pathway and phosphorylated protein kinase A (p-PKA)-phosphorylated cAMP response element binding protein (p-CREB)-brain derived neurotrophic factor (BDNF) axis. It suggested COX-2 might play a critical role in learning, regulating neuronal structure and gamma oscillations in the hippocampus CA1 by regulating COX-2/BDNF signalling pathway.
普遍认为环氧化酶-2（COX-2）的激活会引起炎症。然而，COX-2 也在皮质和脊髓神经元的突触后树突和兴奋性末端持续表达。尽管有一些证据表明，神经元信号传递过程中 COX-2 的释放对于调节记忆功能可能至关重要，但持续表达的 COX-2 在神经元中的意义仍不清楚。本研究旨在发现 COX-2 在神经炎症之外对记忆的作用，并确定抑制 COX-2 是否通过影响树突可塑性及其潜在机制导致认知功能障碍。我们发现 COX-2 基因敲除（KO）可显著影响学习和记忆能力，导致神经元结构紊乱并影响γ 振荡。这可能是通过抑制前列腺素（PG）E2/cAMP 途径和磷酸化蛋白激酶 A（p-PKA）-磷酸化 cAMP 反应元件结合蛋白（p-CREB）-脑源性神经营养因子（BDNF）轴来介导的。这表明 COX-2 可能通过调节 COX-2/BDNF 信号通路在海马 CA1 中发挥关键作用，调节学习、神经元结构和γ 振荡。
