Sildenafil (Viagra®) prevents and restores LPS-induced inflammation in astrocytes

NEUROSCIENCE LETTERS

卷:630

Article

de Santana Nunes, Ana Karolina^1,2  Raposo, Catarina³  Bjorklund, Ulrika⁴  da Cruz-Hofling, Maria Alice⁵  Peixoto, Christina Alves¹  Hansson, Elisabeth⁴ 

[1] Oswaldo Cruz Fdn Fiocruz, Aggeu Magalhaes Res Ctr CPqAM, Lab Ultrastruct, Recife, PE, Brazil

[2] Fed Univ Pernambuco UFPE, Recife, PE, Brazil

[3] Paulista State Univ UNESP, Dept Morphol, BR-14801903 Araraquara, SP, Brazil

[4] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, SE-41345 Gothenburg, Sweden

[5] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP, Brazil

关键词: Phosphodiesterase-5 inhibitor;    Neuroinflammation;    Lipopolysaccharide;    Calcium;    Cytoskeleton;    Sildenafil;   

DOI  :  10.1016/j.neulet.2016.07.029

来源: Elsevier

【 摘 要 】

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 Ca2+ 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 10 mu M for 4h and then sildenafil 1 or 10 mu M + LPS for 24 h. B1: control; B2: LPS for 24 h; B3: LPS for 24 h and then LPS + sildenafil 1 or 10 mu M for 24 h. Cytoskeleton integrity was analyzed through GFAP immunolabeling and actin labeling with an Alexa 488-conjugated phalloidin probe. Calcium responses were assessed through a Ca2+-sensitive fluorophore Fura-2/AM. The results show that both preventive and restorative treatments with sildenafil (in both concentrations) reduced the Ca2+ 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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