title: Sildenafil (Viagra(®)) prevents and restores LPS-induced inflammation in astrocytes.
abstract: Astrocytes are effectively involved in the pathophysiological processes in the central nervous system (CNS) and may contribute to or protect against development of inflammatory and degenerative diseases. Sildenafil is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor, which induces cyclic GMP accumulation. However, the mechanisms of actions on glial cells are not clear. The aim of the present work is to evaluate the role of sildenafil in lipopolysaccharide (LPS)-stimulated astrocytes. The cytoskeleton integrity and Ca(2+) waves were assessed as indicators of inflammatory state. Two main groups were done: (A) one prevention and (B) one restoration. Each of these groups: A1: control; A2: LPS for 24h; A3: sildenafil 1 or 10μM for 4h and then sildenafil 1 or 10μM+LPS for 24h. B1: control; B2: LPS for 24h; B3: LPS for 24h and then LPS+sildenafil 1 or 10μM for 24h. Cytoskeleton integrity was analyzed through GFAP immunolabeling and actin labeling with an Alexa 488-conjugated phalloidin probe. Calcium responses were assessed through a Ca(2+)-sensitive fluorophore Fura-2/AM. The results show that both preventive and restorative treatments with sildenafil (in both concentrations) reduced the Ca(2+) responses in intensity and induced a more organized actin fiber pattern, compared to LPS treated cells. This work demonstrated for the first time that astrocytes are a key part of the sildenafil protective effects in the CNS.
authors.affiliation: Laboratory of Ultrastructure, Aggeu Magalhães Research Center (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, PE, Brazil; Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Ana Karolina
authors.initials: AK
authors.lastname: de Santana Nunes
authors.affiliation: Department of Morphology, Paulista State University (UNESP), 14801-903, Araraquara, SP, Brazil.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rapôso
authors.affiliation: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE 413 45, Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Björklund
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), 13 083-970 Campinas, SP, Brazil.
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
authors.affiliation: Laboratory of Ultrastructure, Aggeu Magalhães Research Center (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, PE, Brazil.
authors.forename: Christina Alves
authors.initials: CA
authors.lastname: Peixoto
authors.affiliation: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE 413 45, Gothenburg, Sweden. Electronic address: elisabeth.hansson@neuro.gu.se.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hansson
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects*; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008070:Lipopolysaccharides; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D051381:Rats; D000068677:Sildenafil Citrate / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D058986:Phosphodiesterase 5 Inhibitors; D000255:Adenosine Triphosphate; D000068677:Sildenafil Citrate
keywords: Calcium; Cytoskeleton; Lipopolysaccharide; Neuroinflammation; Phosphodiesterase-5 inhibitor; Sildenafil