The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia
| Autor: | Masashi Hiramoto, Miwako Shobo, Michael F. Egan, Daniel R. Weinberger, Masatoshi Yuri, Junko Yarimizu, Masato Kobori, Akihiko Fujikawa, Kristin K. Nicodemus, Joseph H. Callicott, Ayako Matsuo, Takeshi Sasayama, Akira Miyake, Masayasu Yoshino, Shun Ichiro Matsumoto, Andreas Meyer-Lindenberg, Kiyoshi Furuichi, Kazuhiro Terai, Hitoshi Matsushime, Masao Katoh, Jun Takasaki, Lucas Kempf, Shintaro Nishimura, Shuji Morita, Hideki Hiyama, Robyn A. Honea, Hiroyuki Ishii, Mitsuyuki Matsumoto, Masazumi Kamohara, Stefano Marenco, Radha Krishna Vakkalanka, Hiroyuki Yokota, Sosuke Miyoshi, Shinji Takahashi, Nobuya Matsuoka, Richard E. Straub, Takatoshi Soga |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Transgene Molecular Sequence Data Nerve Tissue Proteins Hippocampal formation Biology Polymorphism Single Nucleotide Receptors G-Protein-Coupled Evolution Molecular Mice Internal medicine medicine Animals Humans Genetic Predisposition to Disease Amino Acid Sequence Allele Receptor Alleles Genetics Mice Knockout Multidisciplinary Behavior Animal Dentate gyrus Brain Organ Size Biological Sciences medicine.disease Phenotype Magnetic Resonance Imaging Endocrinology Schizophrenia Brain size Schizophrenic Psychology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 105(16) |
| ISSN: | 1091-6490 |
| Popis: | The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3′ UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy. |
| Databáze: | OpenAIRE |
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