title: Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model.
abstract: BACKGROUND
  Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats.
  
  
  METHODS
  Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus.
  
  
  RESULTS
  We found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function.
  
  
  CONCLUSIONS
  We propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan.
authors.forename: Kristian
authors.initials: K
authors.lastname: Liaury
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tsumori
authors.forename: Motohide
authors.initials: M
authors.lastname: Furuya
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.forename: Masa
authors.initials: M
authors.lastname: Ieda
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuchie
authors.forename: Michiyo
authors.initials: M
authors.lastname: Taki
authors.forename: Kotomi
authors.initials: K
authors.lastname: Ishihara
authors.forename: Andi Jayalangkara
authors.initials: AJ
authors.lastname: Tanra
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D018891:Dentate Gyrus / Q000166:cytology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar
chemical_list: C100745:Aif1 protein, rat; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D010751:Phosphopyruvate Hydratase