title: Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model.
abstract: BACKGROUND
  Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and the general healthy population. We examined the hyperbilirubinemia on behavioral and neuropathological changes in rats as a possible animal model of schizophrenia.
  
  
  METHODS
  Gunn rats with severe hyperbilirubinemia (j/j), Gunn rats without severe hyperbilirubinemia (+/j), and Wistar rats were examined by open-field, social interaction, and prepulse inhibition tests. TUNEL, AgNOR and Ki-67 were also assayed on paraffin-embedded brain sections of these rats.
  
  
  RESULTS
  Compared to Wistar rats, both Gunn j/j and +/j rats showed hyperlocomotion, high sniffing scores, and low defecation scores. They showed significantly more aggressive behaviors and impaired prepulse inhibition. The numbers of Ki-67-labeled cells and AgNOR were lower and the number of TUNEL-positive cells was higher than that of Wistar rats.
  
  
  CONCLUSIONS
  These results might support the neurodevelopmental hypothesis of schizophrenia. Both Gunn j/j and +/j rats may be a useful animal model and provide clues to the role of hyperbilirubinemia in schizophrenia.
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Hayashida
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuchie
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yasuda
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.forename: Akira
authors.initials: A
authors.lastname: Nishida
authors.forename: Takuji
authors.initials: T
authors.lastname: Inagaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toga
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nagami
authors.forename: Teiji
authors.initials: T
authors.lastname: Oda
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006932:Hyperbilirubinemia / Q000150:complications*; D020287:In Situ Nick-End Labeling; D007266:Inhibition, Psychological; D007398:Interpersonal Relations; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000150:complications* / Q000473:pathology*; D012565:Schizophrenic Psychology; D012903:Smell / Q000502:physiology
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; C051963:nucleolar organizer region associated proteins