Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders

Hideaki Imai, Hirotaka Shoji, Masaki Ogata, Yoshiteru Kagawa, Yuji Owada, Tsuyoshi Miyakawa, Kenji Sakimura, Toshio Terashima, Yu Katsuyama

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Reelin-Dab1 signaling is involved in brain development and neuronal functions. The abnormalities in the signaling through either reduction of Reelin and Dab1 gene expressions or the genomic mutations in the brain have been reported to be associated with psychiatric disorders. However, it has not been clear if the deficiency in Reelin-Dab1 signaling is responsible for symptoms of the disorders. Here, to examine the function of Reelin-Dab1 signaling in the forebrain,we generated dorsal forebrain-specific Dab1 conditional knockout mouse (Dab1 cKO) and performed a behavioral test battery on the Dab1 cKO mice. Although conventional Dab1 null mutant mice exhibit cerebellar atrophy and cerebellar ataxia, the Dab1 cKO mice had normal cerebellum and showed no motor dysfunction. Dab1 cKO mice exhibited behavioral abnormalities, including hyperactivity, decreased anxiety-like behavior, and impairment of working memory, which are reminiscent of symptoms observed in patients with psychiatric disorders such as schizophrenia and bipolar disorder. These results suggest that deficiency of Reelin-Dab1 signal in the dorsal forebrain is involved in the pathogenesis of some symptoms of human psychiatric disorders.

Original languageEnglish
Pages (from-to)3485-3501
Number of pages17
JournalCerebral Cortex
Volume27
Issue number7
DOIs
Publication statusPublished - 01-07-2017

All Science Journal Classification (ASJC) codes

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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    Imai, H., Shoji, H., Ogata, M., Kagawa, Y., Owada, Y., Miyakawa, T., Sakimura, K., Terashima, T., & Katsuyama, Y. (2017). Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders. Cerebral Cortex, 27(7), 3485-3501. https://doi.org/10.1093/cercor/bhv334