title: Vldlr overexpression causes hyperactivity in rats.
abstract: BACKGROUND
  Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.
  
  
  METHODS
  We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.
  
  
  RESULTS
  Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.
  
  
  CONCLUSIONS
  Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Clinical Pharmacology, Yokohama College of Pharmacy, Yokohama, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Izumo
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Manabe
authors.affiliation: Department of Synthetic Organic Chemistry, Yokohama College of Pharmacy, Yokohama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Institute of Psychology and Behavioral Neuroscience, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ichitani
authors.affiliation: Institute of Psychology and Behavioral Neuroscience, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mahesh Mundalil
authors.initials: MM
authors.lastname: Vasu
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Shimmura
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Wakuda
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kameno
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori