Fluoxetine Ameliorates Depression via Activation of CREB/BDNF/TrkB Pathway in Triple Transgenic Alzheimer's Disease Model Mice

Background and Objective: Alzheimer's Disease (AD) is a neuro degenerative disease associated with neuronal degeneration. Fluoxetine (FLX) is a classical drug used in the treatment of depression in a clinic. However, whether FLX has a therapeutic effect on depression and cognitive deficits in patients with early AD is unknown. This study aimed to study the therapeutic effect and possible mechanism of FLX on depression and cognitive deficits in the early AD model. Materials and Methods: FLX (10 mg kgG1/day) was administered intragastrically once daily for 6 months to the 3-months-old male APPSwe/PS1M146V/tauP301L (3xTg-AD) mice. Behaviour tests were performed in 3 months and 6 months since drug administration. Results: The results showed that FLX significantly improved both recognition and spatial memory, alleviated the anxiety-like behaviour and promoted neuronal survival in 3xTg-AD mice. In addition, FLX could activate cAMP-response Element-binding protein (CREB)/brain-derived Neurotrophic Factor (BDNF)/Tropomyosin-related kinase B (TrkB) signaling. Conclusion: Activation of the CREB/BDNF/TrkB pathway of FLX might be considered a promising therapeutic approach for alleviating the cognitive deficits associated with early AD.