title: Melatonin decreases brain apoptosis, oxidative stress, and CD200 expression and increased survival rate in mice infected by Venezuelan equine encephalitis virus.
abstract: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus.
  
  
  
  Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection. Brain samples were obtained at those periods of time. In addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]: 1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and 6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and TUNEL assay, respectively. Nitrites and malondialdehyde were determined by appropriate biochemical methods.
  
  
  
  Increased brain expression of apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice were found. Melatonin diminished those expressions. Similarly, high apoptosis expression and nitrite and malondialdehyde productions on infected neuroblastoma cultures were diminished by melatonin. Melatonin increased the survival rate (25%) in Venezuelan equine encephalitis virus-infected animals compared with untreated infected mice (0%).
  
  
  
  Neurological damage during brain Venezuelan equine encephalitis virus infection could be mediated by apoptosis and oxidative stress and CD200 molecule could be an important anti-inflammatory response. Melatonin could be beneficial reducing apoptosis and oxidative stress.
authors: Departamento de Microbiologia, Escuela de Bioanalisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Milagros
authors: M
authors: Montiel
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Ernesto
authors: E
authors: Bonilla
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela valero.nereida@gmail.com.
authors: Nereida
authors: N
authors: Valero
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Jesús
authors: J
authors: Mosquera
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Luz M
authors: LM
authors: Espina
authors: Centro de Investigaciones Biomédicas, Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, Venezuela.
authors: Yasmir
authors: Y
authors: Quiroz
authors: Departamento de Enfermedades Inmunitarias y Oncología, Hospital "Príncipe de Asturias," Universidad de Alcalá, Madrid, España.
authors: Melchor
authors: M
authors: Álvarez-Mon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004666:Encephalitis Virus, Venezuelan Equine / Q000472:pathogenicity*; D004685:Encephalomyelitis, Venezuelan Equine / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects*; D015996:Survival Rate
chemical_list: D015703:Antigens, CD; D008550:Melatonin; C042739:antigens, CD200
keywords: CD200; Venezuela equine encephalitis virus; apoptosis; brain; neuroblastoma; survival rate