Cognitive improving actions of tofacitinib in a mouse model of Alzheimer disease involving TNF-α, IL-6, PI3K-Akt and GSK-3β signalling pathway

Aim and Objective: This current study investigated the significance of tofactinib in improving memory functions in a memory model of β-amyloid (Aβ)-induced dementia.Material and Methods: Aβ1-42 was injected in the brain of mice using intracerebroventricular injection and after 14 days, the learning and memory was assessed on the Morris Water maze test. Mice were treated with tofactinib (10, 20, 30 mg/kg) two days prior to Aβ1-42 injection and 14 days after Aβ injection.Results: Treatment of tofactinib significantly improved the learning (decrease in day escape latency time [ELT]) and memory (increase in time spent in target quadrant). This drug also decreased the levels of T NF-α and IL-6 along with the rise in expression of p-Akt and p-GSK-3β/GSK-3β ratio in mice brain. Co-administration of LY294002 (P I3K inhibitor) or MK-2206 2HCl (Akt inhibitor) with tofactinib (30 mg/kg) obliterated the beneficial effects of the latter by increasing T NF-α and IL-6 levels along with decreasing the p-Akt expression and p-GSK-3β/GSK-3β ratio.Conclusion: It is concluded that tofactinib improves the condition of dementia of Alzheimer's type, possibly through down regulation of T NF-α and IL-6 and instigation of P I3K-Akt-p-GSK-3β signalling system in the hippocampus of Aβ-treated mice.