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.
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