The crucial role that hippocampus Cyclooxygenase-2 plays in memory

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.

Keywords: BDNF; COX-2; gamma oscillations; memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor* / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Hippocampus* / metabolism
  • Learning
  • Signal Transduction


  • Cyclooxygenase 2
  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein