Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders

Miwako Kobayashi, Toshiyuki Nakatani, Toshiaki Koda, Ken Ichi Matsumoto, Ryosuke Ozaki, Natsuki Mochida, Keizo Takao, Tsuyoshi Miyakawa, Ichiro Matsuoka

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system. Results: Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD). Conclusions: Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

Original languageEnglish
Article number12
JournalMolecular Brain
Volume7
Issue number1
DOIs
Publication statusPublished - 14-02-2014

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Neurogenesis
Psychiatry
Dentate Gyrus
Parvalbumins
Aptitude
Neural Stem Cells
Social Behavior
Interneurons
Locomotion
Attention Deficit Disorder with Hyperactivity
Interpersonal Relations
Short-Term Memory
Nervous System
Hippocampus
Schizophrenia
Cell Cycle
Anxiety
Brain
Population
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Kobayashi, Miwako ; Nakatani, Toshiyuki ; Koda, Toshiaki ; Matsumoto, Ken Ichi ; Ozaki, Ryosuke ; Mochida, Natsuki ; Takao, Keizo ; Miyakawa, Tsuyoshi ; Matsuoka, Ichiro. / Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders. In: Molecular Brain. 2014 ; Vol. 7, No. 1.
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abstract = "Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system. Results: Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD). Conclusions: Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.",
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Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders. / Kobayashi, Miwako; Nakatani, Toshiyuki; Koda, Toshiaki; Matsumoto, Ken Ichi; Ozaki, Ryosuke; Mochida, Natsuki; Takao, Keizo; Miyakawa, Tsuyoshi; Matsuoka, Ichiro.

In: Molecular Brain, Vol. 7, No. 1, 12, 14.02.2014.

Research output: Contribution to journalArticle

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AU - Kobayashi, Miwako

AU - Nakatani, Toshiyuki

AU - Koda, Toshiaki

AU - Matsumoto, Ken Ichi

AU - Ozaki, Ryosuke

AU - Mochida, Natsuki

AU - Takao, Keizo

AU - Miyakawa, Tsuyoshi

AU - Matsuoka, Ichiro

PY - 2014/2/14

Y1 - 2014/2/14

N2 - Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system. Results: Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD). Conclusions: Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

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