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 language | English |
|---|---|
| Pages (from-to) | 3485-3501 |
| Number of pages | 17 |
| Journal | Cerebral Cortex |
| Volume | 27 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 01-07-2017 |
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All Science Journal Classification (ASJC) codes
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience
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Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders. / Imai, Hideaki; Shoji, Hirotaka; Ogata, Masaki; Kagawa, Yoshiteru; Owada, Yuji; Miyakawa, Tsuyoshi; Sakimura, Kenji; Terashima, Toshio; Katsuyama, Yu.
In: Cerebral Cortex, Vol. 27, No. 7, 01.07.2017, p. 3485-3501.Research output: Contribution to journal › Article
TY - JOUR
T1 - Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders
AU - Imai, Hideaki
AU - Shoji, Hirotaka
AU - Ogata, Masaki
AU - Kagawa, Yoshiteru
AU - Owada, Yuji
AU - Miyakawa, Tsuyoshi
AU - Sakimura, Kenji
AU - Terashima, Toshio
AU - Katsuyama, Yu
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85024391162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024391162&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhv334
DO - 10.1093/cercor/bhv334
M3 - Article
C2 - 26762856
AN - SCOPUS:85024391162
VL - 27
SP - 3485
EP - 3501
JO - Cerebral Cortex
JF - Cerebral Cortex
SN - 1047-3211
IS - 7
ER -