Parvalbumin-positive GABAergic interneurons deficit in the hippocampus in Gunn rats: A possible hyperbilirubinemia-induced animal model of schizophrenia
Maiko Hayashida,
Tsuyoshi Miyaoka,
Keiko Tsuchie,
Tomoko Araki,
Muneto Izuhara,
Shoko Miura,
Misako Kanayama,
Koji Ohtsuki,
Michiharu Nagahama,
Ilhamuddin Abdul Azis,
Rostia Arianna Abdullah,
Muhammad Alim Jaya,
Ryosuke Arauchi,
Sadayuki Hashioka,
Rei Wake,
Toshiko Tsumori,
Jun Horiguchi,
Arata Oh-Nishi,
Masatoshi Inagaki
Affiliations
Maiko Hayashida
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan; Corresponding author.
Tsuyoshi Miyaoka
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Keiko Tsuchie
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Tomoko Araki
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Muneto Izuhara
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Shoko Miura
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Misako Kanayama
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Koji Ohtsuki
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Michiharu Nagahama
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Ilhamuddin Abdul Azis
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Rostia Arianna Abdullah
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Muhammad Alim Jaya
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Ryosuke Arauchi
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Sadayuki Hashioka
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Rei Wake
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
Toshiko Tsumori
Department of Nursing, Faculty of Health and Welfare, Prefectural University of Hiroshima, Japan
Jun Horiguchi
Division of Immune-Neuropsychiatry, Faculty of Medicine, Shimane University, Japan
Arata Oh-Nishi
Division of Immune-Neuropsychiatry, Faculty of Medicine, Shimane University, Japan; RESVO Inc., Japan
Masatoshi Inagaki
Department of Psychiatry, Faculty of Medicine, Shimane University, Japan
A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. Importantly, these alterations in GABAergic neurons are not global, which means they are more prevalent among distinct subclasses of interneurons, including those that express the calcium binding protein parvalbumin.A decreased expression of parvalbumin in the hippocampus is a consistent observation not only in postmortem human schizophrenia patients, but also in a diverse number of rodent models of the disease.Meanwhile, previously we reported that the congenital hyperbilirubinemia model rats (Gunn rats), which is a mutant of the Wistar strain, showed behavioral abnormalities, for instance, hyperlocomotor activity, deficits of prepulse inhibition, inappropriate social interaction, impaired recognition memory similar with several rodent models of schizophrenia. Several animal studies linked the importance of palvalbumin in relation to abnormal hippocampal activity and schizophrenia-like behavior.Here, we show that parvalbumin positive cell density was significantly lower in the CA1, CA3 and the total hippocampus of Gunn rats (congenital hyperbilirubinemia model rats) compared to Wistar control rats. The correlations between serum UCB levels and loss of PV expression in the hippocampus were also detected. The decreases in the PV-expression in the hippocampus might suggest an association of the behavioral abnormalities as schizophrenia-like behaviors of Gunn rats, compared to the Wistar control rats.
