title: Hypercholesterolemia as a risk factor for depressive disorder?
abstract: OBJECTIVE
  Epidemiological findings demonstrated that increased plasma cholesterol levels are frequently observed in depressive patients. In this regard, there is enhancing evidence that hypercholesterolemia is associated with impairment of brain function. Recently, we demonstrated that low-density lipoprotein receptor knockout (LDLr(-/-)) mice- a widely used rodent model of familial hypercholesterolemia - exhibited memory deficits and cortico-cerebral mitochondrial dysfunction. In this study, we aimed to assess the hypercholesterolemic mice in predictive tasks for depressive-like behavior.
  
  
  METHODS
  Adult wild type C57BL/6 and LDLr (-/-) mice were evaluated in two tests for depressive like behavior, the splash test and forced swimming test. In addition, the activity of monoamine oxidase isoforms and the mRNA levels of hemeoxygenase-1 were assessed in the hippocampus and cerebral cortex of C57BL/6 and LDLr (-/-) mice. Finally, the blood-brain-barrier (BBB) permeability was investigated using the AQP-4 immunofluorescence staining in the mice hippocampus.
  
  
  RESULTS
  The LDLr (-/-) mice showed a significant reduction in the grooming time in the splash test and increased immobility time in the forced swimming test, and both parameters were reversed by fluoxetine antidepressant treatment (10mg/kg, 7 days, o.g.). Interestingly, the depressive like behavior of LDLr (-/-) mice was associated with increased activity of monoamine oxidase A, decreased hemeoxygenase-1 mRNA levels and increase of BBB permeability in the hippocampus.
  
  
  CONCLUSIONS
  Overall, these data provide new evidence that hypercholesterolemia could trigger brain alterations involved in depressive disorders.
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.. Electronic address: andreza.bem@ufsc.br.
authors.forename: A
authors.initials: A
authors.lastname: De Bem
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Engel
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: J
authors.initials: J
authors.lastname: de Oliveira
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: E L G
authors.initials: EL
authors.lastname: Moreira
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: V B
authors.initials: VB
authors.lastname: Neis
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: D B
authors.initials: DB
authors.lastname: Santos
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Lopes
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: A L S
authors.initials: AL
authors.lastname: Rodrigues
authors.affiliation: Campus Universitário Trindade (Centro de Ciências Biológica), Departamento de Bioquímica, Florianópolis - Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Brocardo