Pharmacological effects of Ibuprofen on learning and memory, muscarinic receptors gene expression and APP isoforms level in pre-frontal cortex of AlCl₃-induced toxicity mouse model

Abstract

Aluminium metal (Al) has been implicated in the etiology of many neurodegenerative diseases, most commonly the Alzheimer's disease (AD). Al causes biochemical defects by affecting the neurotransmitters level, causes conformational changes in amyloid β protein and increases amyloid accumulation in brain. Aim: This study was aimed at evaluating neuroprotective effect of Ibuprofen (IBU) (25 mg/kg/day for 12 days) in AlCl₃-induced (150 mg/kg/day for 12 days) toxicity. Methods: Treated mice were subjected to learning and memory tests. Cholinergic muscarinic receptors (mAChR; M1-M5) and APP isoforms (APP695, APP770 and APP common) gene expression were carried out from the pre-frontal cortex area. Results: Profound effect on learning and memory was observed in IBU treated group along with enhanced expression of M1 mAChR (0.40 ± 0.03; p < 0.01) compared to AlCl₃-induced toxicity group (0.05 ± 0.02). Fear memory was improved in IBU treated group (89.68 ± 2.58, p < 0.01) as compared to AlCl₃-induced toxicity group (54.58 ± 8.21). Discrimination index in social novelty test in IBU treated group was improved (81.13 ± 8.71; p < 0.05), compared to AlCl₃-induced toxicity group (46.28 ± 5.55). Similarly, recognition memory of IBU treated group in novel object recognition test (NOB) was retained (66.85 ± 5.60; p < 0.05) as compared to AlCl₃-induced toxicity group (33.06 ± 11.80). Conclusion: IBU demonstrated memory enhancing effect, however, its effect on the APP isoforms expression in pre-frontal cortex needs further studies.

KEYWORDS:

• pre-frontal cortex
• Ibuprofen
• social memory
• muscarinic receptors
• APP
• cholinergic hypfunction

Declaration of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

This study was supported by Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Pakistan and from the Small Research Project Grants (SRPG) 2012, College of Medicine, Alfaisal University. IRG No. 313090202133.