title: Neuropeptide Y neuronal network dysfunction in the frontal lobe of a genetic mouse model of schizophrenia.
abstract: Neuropeptide Y (NPY) has been found to play a critical role in various mental functions as a neurotransmitter and is involved in the development of schizophrenia, a particularly intractable psychiatric disease whose precise etiology remains unknown. Recent molecular biological investigations have identified several candidate genes which may be associated with this disease, including disrupted-in-schizophrenia 1 (DISC1). The role of DISC1 would involve neurogenesis and neuronal migration. However, the functional consequences of this gene defect have not yet been fully clarified in neuronal systems. In the present study, to clarify the neuropathological changes associated with the function of DISC1, we explored how DISC1 dysfunction can induce abnormalities in the NPY neuronal network in the central nervous system. We performed immunohistochemical analyses (including the observation of the distribution and density) of prefrontal cortex specimens from DISC1-knockout (KO) mice, which are considered to be a novel animal model of schizophrenia. We then evaluated the number and size of NPY-immunoreactive (NPY-IR) neurons and the length of NPY-IR fibers. The number of NPY-IR neurons and the length of the fibers were decreased in the prefrontal cortex of DISC1-KO mice. The decrease was particularly prominent in the superficial regions, and the distribution of NPY-IR neurons differed between wild-type and DISC1-KO mice. However, the size of the neurons in the cortices of the DISC1-KO and wild-type mice did not differ markedly. Our findings suggest that dysfunction of DISC1 may lead to the alteration of NPY neurons and neurotransmission issues in NPY-containing neuron systems, which seem to play important roles in both the mental function and neuronal development. DISC1 dysfunction may be involved in the pathogenesis of schizophrenia through the impairment of the NPY neuronal network.
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: smorosawa1@gmail.com.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Morosawa
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: iritani@med.nagoya-u.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Iritani
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: fujishiro1975@gmail.com.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Fujishiro
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: S-guchi@amber.plala.or.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: youtat@med.nagoya-u.ac.jp.
authors.forename: Youta
authors.initials: Y
authors.lastname: Torii
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: habuchi@hm9.aitai.ne.jp.
authors.forename: Chikako
authors.initials: C
authors.lastname: Habuchi
authors.affiliation: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: k-kuroda@med.nagoya-u.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: kaibuchi@med.nagoya-u.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: ozaki-n@med.nagoya-u.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000503:physiopathology; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y
keywords: Animal model; DISC1 (disrupted-in-schizophrenia 1); Immunohistochemistry; Prefrontal cortex; Schizophrenia