title: Modulation of microglial function by the antidepressant drug venlafaxine.
abstract: An increasing amount of data suggests that depression is an inflammatory disease. Depressed patients have higher peripheral blood levels of inflammatory markers which have been shown to access the brain and interact with the pathophysiological domain known to be involved in depression. Furthermore, microglia activation may play an important role in the inflammatory pathophysiology of depression. In BV-2 microglia cell line, the present study investigated the potential anti-inflammatory effects of venlafaxine, along with its potential influence on injury of lipopolysaccharide (LPS)-stimulated cells. Although venlafaxine showed only marginal influence on the majority of the pro-inflammatory parameters assessed (in particular NO release, phagocytosis and proliferation), it significantly suppressed superoxide production by the stimulated cells. In addition, venlafaxine exerted also a protective effect on mitochondrial membrane potential and lysosomes of the stimulated microglia. In conclusion, our results suggest that although VEN might have only a marginal effect on major pro-inflammatory parameters of microglia, its inhibitory effect on superoxide generation can contribute to the prevention of harmful effects of oxidative and nitrosative stress involved in the pathogenesis of depression. Moreover, the protective effect of VEN on viability of microglia can prevent a rapid reduction of these cells, thus avoiding limitations of several physiological processes in the brain and possibly also the progression of depression.
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Department of Developmental and Behavioral Toxicology, Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Dubovický
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Department of Developmental and Behavioral Toxicology, Bratislava, Slovakia.
authors.forename: Eszter
authors.initials: E
authors.lastname: Császár
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Department of Developmental and Behavioral Toxicology, Bratislava, Slovakia.
authors.forename: Kristína
authors.initials: K
authors.lastname: Melicherčíková
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Kuniaková
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Department of Developmental and Behavioral Toxicology, Bratislava, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Račková
keywords: cytoprotection; depression; inflammation; microglia; venlafaxine