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.
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.


OBJECTIVE
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).


CONCLUSIONS
IBU demonstrated memory enhancing effect, however, its effect on the APP isoforms expression in pre-frontal cortex needs further studies.
1Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology , Islamabad , Pakistan.
Aisha Nasir
AN
Hashmi
Ahmed
A
Yaqinuddin
Touqeer
T
Ahmed
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001252:Astringents / Q000633:toxicity; D002712:Chlorides / Q000633:toxicity; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D005239:Fear; D005786:Gene Expression Regulation / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009425:Nesting Behavior / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior
D017607:Aluminum Compounds; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001252:Astringents; D002712:Chlorides; D011976:Receptors, Muscarinic; D000077410:Aluminum Chloride; D007052:Ibuprofen
APP; Ibuprofen; cholinergic hypfunction; muscarinic receptors; pre-frontal cortex; social memory