title: Neuroprotective and procognitive effects of sertraline: in vitro and in vivo studies.
abstract: Selective serotonin reuptake inhibitors (SSRIs) stimulate synaptic plasticity and neurogenesis, most likely via the MAP-kinase signal transduction pathway (by phosphorilation of ERK) and by stimulating neurotrophic factors such as brain derived neurotrophic factor (BDNF) and the neuroprotective protein (Bcl-2). Using human neuroblastoma cells (SHSY5Y), we found that sertraline and its derivative, desmethylsertraline, at low concentrations (1-10 μM), induced potent neurotrophic activity. Subsequently, we have treated for 21 days young and aged mice with sertraline. Sertraline in certain doses improved significantly spatial memory learning, in both young and old mice. Sertraline treatment resulted in up-regulation of brain BDNF, phospho-ERK and Bcl-2 that may be involved in the pro-cognitive effect of sertraline.
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel Aviv University, Israel. michalt@post.tau.ac.il
authors.forename: Michal
authors.initials: M
authors.lastname: Taler
authors.forename: Oded
authors.initials: O
authors.lastname: Miron
authors.forename: Irit
authors.initials: I
authors.lastname: Gil-Ad
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020280:Sertraline / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: BDNF; Cognition; Neuroprotection; Selective serotonin reuptake inhibitors; Sertraline