title: Cyclooxygenase I and II inhibitors distinctly enhance hippocampal- and cortex-dependent cognitive functions in mice.
abstract: Cyclooxygenase (COX) enzymes are expressed in the brain; however, their role in hippocampus-dependent and cortex-dependent cognitive functions remains to be fully elucidated. The aim of the present study was to comparatively investigate the effects of piroxicam, a selective COX-I inhibitor, and celecoxib, a selective COX‑II inhibitor, on cognitive functions in an AlCl3‑induced neurotoxicity mouse model to understand the specific role of each COX enzyme in the hippocampus and cortex. The AlCl3 (250 mg/kg) was administered to the mice in drinking water and the drugs were administered in feed for 30 days. Assessments of memory, including a Morris water maze, social behavior and nesting behavior were performed in control and treated mice. The RNA expression of the COX enzymes were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis. An ex‑vivo 2,2‑Diphenyl‑1‑picrylhydrazyl assay was performed in the hippocampus and cortex. Following 30 days of treatment with thedrugs, the mice in the celecoxib‑ and piroxicam‑treated groups exhibited enhanced learning (6.84 ± 0.76 and 9.20 ± 1.08, respectively), compared with the AlCl3‑induced neurotoxicity group (21.14 ± 0.76) on the fifth day of the Morris water maze test. Celecoxib treatment improved social affiliation in the AlCl3‑induced neurotoxicity group, the results of which were superior to piroxicam. Piroxicam led to better improvement in nesting score in the AlCl3‑induced neurotoxicity group. Both drugs decreased the expression levels of COX‑I and COX‑II in the hippocampus and cortex, and rescued oxidative stress levels. These findings suggested that each drug distinctly affected cognitive functions, highlighting the distinctive roles of COX-I and COX-II in learning and memory.
authors.affiliation: Neurobiology Laboratory, Atta‑ur‑Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Syed
authors.affiliation: College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
authors.forename: Muhammad Faisal
authors.initials: MF
authors.lastname: Ikram
authors.affiliation: College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Yaqinuddin
authors.affiliation: Neurobiology Laboratory, Atta‑ur‑Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D002712:Chlorides; D003071:Cognition / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D010894:Piroxicam / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D000077410:Aluminum Chloride; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib