Amitriptyline Protects Against Lidocaine-induced Neurotoxicity in SH-SY5Y Cells via Inhibition of BDNF-mediated Autophagy

摘要: Amitriptyline (AMI) is a traditional tricyclic antidepressant that has been proven to exhibit neuroprotective effects in various neurological disorders. However, the underlying mechanism by which AMI attenuates lidocaine-induced neurotoxicity remains poorly understood. Brain-derived neurotrophic factor (BDNF) an essential neurotrophin neuronal development and survival brain, recent studies have suggested BDNF plays important role mediating neurotoxicity. The present study was performed evaluate protective effect of against induced lidocaine explore BDNF-dependent autophagy this process. data showed pretreatment alleviated neurotoxicity, as evidenced restoration cell viability, normalization morphology, reduction apoptosis index. In addition, inhibitor 3-methyladenine (3-MA) had similar AMI, but activator rapamycin eliminated suppressing mTOR activation. Moreover, at molecular level, we found AMI-mediated involved expression BDNF. overexpression or application exogenous recombinant significantly suppressed protected SH-SY5Y cells from Lido, whereas neuroprotection abolished either knockdown use tropomyosin-related kinase B (TrkB) ANA-12 cells. Overall, our findings demonstrated correlated with inhibition activity through upregulation expression.