Vldlr overexpression causes hyperactivity in rats

• Main Authors: Iwata Keiko, Izumo Nobuo, Matsuzaki Hideo, Manabe Takayuki, Ishibashi Yukiko, Ichitani Yukio, Yamada Kazuo, Thanseem Ismail, Anitha Ayyappan, Vasu Mahesh, Shimmura Chie, Wakuda Tomoyasu, Kameno Yosuke, Takahashi Taro, Iwata Yasuhide, Suzuki Katsuaki, Nakamura Kazuhiko, Mori Norio
• Format: Article
• Language: English
• Published: BMC 2012-10-01
• Series: Molecular Autism
• Subjects: Hyperactivity; Neurodevelopmental disorder; Psychiatric disorder; Reelin; Transgenic rat; Vldlr
• Online Access: http://www.molecularautism.com/content/3/1/11

<p>Abstract</p> <p>Background</p> <p>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 <it>VLDLR</it> mRNA levels are increased in the post-mortem brain of autistic patients.</p> <p>Methods</p> <p>We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>