Antioxidant Activity of Fluoxetine and Vortioxetine in a Non-Transgenic Animal Model of Alzheimer’s Disease

Frontiers in Pharmacology

Nicolò Musso²  Federica Geraci²  Annamaria Fidilio²  Filippo Drago²  Salvatore Salomone²  Maria Rosaria Tropea²  Gian Marco Leggio²  Sebastiano Alfio Torrisi²  Daniela Puzzo²  Anna Privitera³  Giuseppe Caruso³  Fabio Tascedda⁴  Margherita Grasso⁵  Filippo Caraci⁵ 

[1] Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy;Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy;Department of Drug and Health Sciences, University of Catania, Catania, Italy;Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;Oasi Research Institute—IRCCS, Troina, Italy;

关键词: oxidative stress;    Alzheimer’s disease;    depression;    amyloid-β;    vortioxetine;    fluoxetine;   

DOI  :  10.3389/fphar.2021.809541

来源: DOAJ

【 摘 要 】

Depression is a risk factor for the development of Alzheimer’s disease (AD). A neurobiological and clinical continuum exists between AD and depression, with neuroinflammation and oxidative stress being involved in both diseases. Second-generation antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are currently investigated as neuroprotective drugs in AD. By employing a non-transgenic AD model, obtained by intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ) oligomers in 2-month-old C57BL/6 mice, we recently demonstrated that the SSRI fluoxetine (FLX) and the multimodal antidepressant vortioxetine (VTX) reversed the depressive-like phenotype and memory deficits induced by Aβ oligomers rescuing the levels of transforming growth factor-β1 (TGF-β1). Aim of our study was to test FLX and VTX for their ability to prevent oxidative stress in the hippocampus of Aβ-injected mice, a brain area strongly affected in both depression and AD. The long-term intraperitoneal (i.p.) administration of FLX (10 mg/kg) or VTX (5 and 10 mg/kg) for 24 days, starting 7 days before Aβ injection, was able to prevent the over-expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (Nox2) induced by Aβ oligomers. Antidepressant pre-treatment was also able to rescue the mRNA expression of glutathione peroxidase 1 (Gpx1) antioxidant enzyme. FLX and VTX also prevented Aβ-induced neurodegeneration in mixed neuronal cultures treated with Aβ oligomers. Our data represent the first evidence that the long-term treatment with the antidepressants FLX or VTX can prevent the oxidative stress phenomena related to the cognitive deficits and depressive-like phenotype observed in a non-transgenic animal model of AD.

【 授权许可】

Unknown