The Crucial Role of Hippocampus Cyclooxygenase-2 Plays in Synaptic Plasticity and Memory

Abstract

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 signaling 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. The cognitive ability was assessed by novel object recognition task (NORT) and Morris water maze (MWM) test. Immunofluorescence, Golgi-cox staining were used to observe dendritic synaptic. Gamma oscillation in hippocampus CA1 was performed by Tetrode in-vivo recording. Prostaglandins were measured by HPLC/mass spectrometry. We observed the expressions of cAMP/ BDNF pathway proteins in hippocampus and N2a cells by Elisa and western blot. We found COX-2 gene knockout could significantly impact the learning and memory ability; reduce the expression of PSD95 in the neuron; cause synaptic disorder; influence gamma oscillation and reduce the expression PGE2, cAMP, p-PKA, p-CREB and BDNF in the hippocampus. It suggests COX-2 may play a critical role in learning and memory ability in modulating postsynaptic membrane PSD95, regulating synaptic plasticity and gamma oscillation in the hippocampus CA1 by regulating COX-2/BDNF signaling pathway.