Cyclooxygenase-2 inhibition affects the expression of down syndrom cell adhesion molecule via interaction with metabotropic glutamate receptor 5

J Physiol Pharmacol. 2022 Apr;73(2). doi: 10.26402/jpp.2022.2.15. Epub 2022 Sep 29.ABSTRACTSince we previously discovered that simultaneous inhibition of cyclooxygenase-2 (COX-2; a highly inducible enzyme, crucial for the conversion of arachidonic acid to prostaglandin G2, which plays a predominant role in the CNS) by NS398 and metabotropic glutamate receptor 5 (mGluR5) through the use of its antagonist [3-((2-methyl-4-thiazolyl)ethyl)pyridine; MTEP] alters mouse behavior (e.g., affects spatial learning, and induces/intensifies the antidepressant effect), our aim was to discover the mechanism responsible for these changes. Down syndrome cell adhesion molecule (DSCAM), a member of the immunoglobulin cell adhesion molecule (Ig-CAM) superfamily, is involved in developing the central and peripheral nervous system by influencing cell adhesion mechanisms necessary for synaptic activity and plasticity. Since COX-2 has been implicated in several neuropsychiatric diseases (e.g., major depressive disorder) resulting from neuroplasticity disorders, and on the other hand, its expression is regulated by synaptic activity, we hypothesized that cognitive changes after administration of COX-2 inhibitor and mGluR5 antagonist might be a consequence of impaired DSCAM expression. Importantly, DSCAM deficiency leads to dysregulation of glutamatergic transmission and plasticity. In previous studies, we have demonstrated glutamatergic changes after NS398 and MTEP administration, further supporting ...
Source: J Physiol Pharmacol - Category: Drugs & Pharmacology Authors: Source Type: research