NEUROBEHAVIORAL AND NEUROCHEMICAL EVALUATION OF EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITOR –GEFITINIB IN Β-AMYLOID OLIGOMER INDUCED ALZHEIMER'S DISEASE IN MICE MODEL
Abstract
Background:Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for about 60-80% of dementia cases globally.Currently used AD drugs provide only symptomatic management with lots of adverse effects. A drug with potential curative for AD with negligible adverse effects remains to be investigated. Gefitinib (GE) is anepidermal growth factor receptor(EGFR) inhibitor, commonly used as monotherapy innon-small cell lung cancer and other solid tumours. Very few studies have shown the memory rescuing capacity of GE.Aim: Therefore the present study was designed to investigate the neuroprotective effect of EGFR inhibitor - GEthrough neurobehavioral and neurochemical analysis in A????1-42oligomer induced AD in a mice model. Methods:AD induction was done by intracerebroventricular (i.c.v.) injection of A????1-42 oligomer (4 μg/4 μl) into the lateral ventricles of mice brain. The test compounds i.e.,GE (2 and 4 mg/kg of body weight) was administered orally on day 10, 13, 16, 19, 22, 25, and 28; and reference drug i.e., donepezil (DP, 2 mg/kg) were administered orally from the 10th to 28th days. The AD-associated neurobehavioral changes were evaluated by the novel object recognition test (NORT) and the neurochemical biomarkeri.e.,neuron-specific enolase (NSE) levels were estimated from brain hippocampal, cortex, and cerebellar samples. Results: The administration of GE was shown to ameliorate the A????1-42 induced neurobehavioral and neurochemical changes. These results were similar to the reference drug donepezil-treated group. Conclusion:EGFRinhibitor -Gefitinib ameliorates the A????1-42 induced AD pathology via multiple molecular pathways.
