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The Crucial Role of Hippocampus Cyclooxygenase-2 Plays in Synaptic Plasticity and Memory
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  • Hong Ni,
  • Zhongzhao Guo,
  • Yue Wu,
  • Jie Wang,
  • Zilu Zhu,
  • Yang Yang,
  • Deheng Wang
Hong Ni
Shanghai University of Traditional Chinese Medicine
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Zhongzhao Guo
Shanghai University of Traditional Chinese Medicine
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Yue Wu
Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine
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Jie Wang
Shuguang Hospital
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Zilu Zhu
Shanghai University of Traditional Chinese Medicine
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Yang Yang
Shanghai University of TCM
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Deheng Wang
Shanghai University of Traditional Chinese Medicine

Corresponding Author:[email protected]

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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 cyclic adenosine monophosphate (cAMP)/ brain-derived neurotrophic factor (BDNF) pathway proteins in hippocampus and N2a cells by Elisa and western blot. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability; reduce the expression of postsynaptic density protein 95 (PSD95) in the neuron; cause synaptic disorder; influence gamma oscillation and reduce the expression prostaglandin (PG) E2, cAMP, phosphorylated protein kinase A (p-PKA), phosphorylated cAMP response element binding protein (p-CREB) and BDNF in the hippocampus. It suggested COX-2 might play a critical role in learning, regulating synaptic plasticity and gamma oscillation in the hippocampus CA1 by regulating COX-2/BDNF signaling pathway.
25 May 2023Submitted to European Journal of Neuroscience
26 May 2023Review(s) Completed, Editorial Evaluation Pending
26 May 2023Submission Checks Completed
26 May 2023Assigned to Editor
26 May 2023Reviewer(s) Assigned
24 Jul 2023Editorial Decision: Revise Minor
19 Sep 20231st Revision Received
19 Sep 2023Review(s) Completed, Editorial Evaluation Pending
19 Sep 2023Submission Checks Completed
19 Sep 2023Assigned to Editor
26 Sep 2023Editorial Decision: Accept