Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model.
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.
Hayashida
Maiko
M
Department of Psychiatry, Shimane University Faculty of Medicine, Japan.
Miyaoka
Tsuyoshi
T
Tsuchie
Keiko
K
Yasuda
Hideaki
H
Wake
Rei
R
Nishida
Akira
A
Inagaki
Takuji
T
Toga
Tomoko
T
Nagami
Haruhiko
H
Oda
Teiji
T
Horiguchi
Jun
J
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
D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; C051963:nucleolar organizer region associated proteins