title: Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders.
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.
authors: Miwako
authors: M
authors: Kobayashi
authors: Toshiyuki
authors: T
authors: Nakatani
authors: Toshiaki
authors: T
authors: Koda
authors: Ken-Ichi
authors: K
authors: Matsumoto
authors: Ryosuke
authors: R
authors: Ozaki
authors: Natsuki
authors: N
authors: Mochida
authors: Keizo
authors: K
authors: Takao
authors: Tsuyoshi
authors: T
authors: Miyakawa
authors: Laboratory of Physiological Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. imatsuok@cc.matsuyama-u.ac.jp.
authors: Ichiro
authors: I
authors: Matsuoka
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000378:metabolism; D005106:Exploratory Behavior; D018390:Gene Targeting; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000473:pathology; D018782:Maze Learning; D008570:Memory, Short-Term; D001523:Mental Disorders / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000378:metabolism; D055495:Neurogenesis; D010320:Parvalbumins / Q000378:metabolism; D012919:Social Behavior
chemical_list: C491992:BRINP1 protein, mouse; D015415:Biomarkers; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins