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SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.(Report)

To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08180.x/abstract Byline: Qian Chen(1), Jeffrey H. Kogan(1), Adam K. Gross(1), Yuan Zhou(2), Noah M. Walton(1), Rick Shin(1), Carrie L. Heusner(1), Shinich... Full description

Journal Title: European Journal of Neuroscience Sept, 2012, Vol.36, p.2597(12)
Main Author: Chen, Qian
Other Authors: Kogan, Jeffrey H. , Gross, Adam K. , Zhou, Yuan , Walton, Noah M. , Shin, Rick , Heusner, Carrie L. , Miyake, Shinichi , Tajinda, Katsunori , Tamura, Kouichi , Matsumoto, Mitsuyuki
Format: Electronic Article Electronic Article
Language: English
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Quelle: Cengage Learning, Inc.
ID: ISSN: 0953-816X
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title: SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.(Report)
format: Article
creator:
  • Chen, Qian
  • Kogan, Jeffrey H.
  • Gross, Adam K.
  • Zhou, Yuan
  • Walton, Noah M.
  • Shin, Rick
  • Heusner, Carrie L.
  • Miyake, Shinichi
  • Tajinda, Katsunori
  • Tamura, Kouichi
  • Matsumoto, Mitsuyuki
subjects:
  • Schizophrenia -- Risk Factors
  • Neurons
  • Immunohistochemistry
  • Cognition
ispartof: European Journal of Neuroscience, Sept, 2012, Vol.36, p.2597(12)
description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08180.x/abstract Byline: Qian Chen(1), Jeffrey H. Kogan(1), Adam K. Gross(1), Yuan Zhou(2), Noah M. Walton(1), Rick Shin(1), Carrie L. Heusner(1), Shinichi Miyake(1), Katsunori Tajinda(1), Kouichi Tamura(1), Mitsuyuki Matsumoto(1) Keywords: bromodeoxyuridine; cognition; dentate gyrus; mutant mouse; psychiatric disease Abstract SREB2/GPR85, a member of the super-conserved receptor expressed in brain (SREB) family, is the most conserved G-protein-coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over-expression) and knockout (KO, null-mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y-maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients. Author Affiliation: (1)CNS, Astellas Research Institute of America LLC, Skokie, IL 60077, USA (2)Master of Biotechnology Program, Northwestern University, Evanston, IL, USA Correspondence: (*) Qian Chen and Mitsu
language: English
source: Cengage Learning, Inc.
identifier: ISSN: 0953-816X
fulltext: fulltext
issn:
  • 0953-816X
  • 0953816X
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titleSREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.(Report)
creatorChen, Qian ; Kogan, Jeffrey H. ; Gross, Adam K. ; Zhou, Yuan ; Walton, Noah M. ; Shin, Rick ; Heusner, Carrie L. ; Miyake, Shinichi ; Tajinda, Katsunori ; Tamura, Kouichi ; Matsumoto, Mitsuyuki
ispartofEuropean Journal of Neuroscience, Sept, 2012, Vol.36, p.2597(12)
identifierISSN: 0953-816X
subjectSchizophrenia -- Risk Factors ; Neurons ; Immunohistochemistry ; Cognition
descriptionTo purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08180.x/abstract Byline: Qian Chen(1), Jeffrey H. Kogan(1), Adam K. Gross(1), Yuan Zhou(2), Noah M. Walton(1), Rick Shin(1), Carrie L. Heusner(1), Shinichi Miyake(1), Katsunori Tajinda(1), Kouichi Tamura(1), Mitsuyuki Matsumoto(1) Keywords: bromodeoxyuridine; cognition; dentate gyrus; mutant mouse; psychiatric disease Abstract SREB2/GPR85, a member of the super-conserved receptor expressed in brain (SREB) family, is the most conserved G-protein-coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over-expression) and knockout (KO, null-mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y-maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients. Author Affiliation: (1)CNS, Astellas Research Institute of America LLC, Skokie, IL 60077, USA (2)Master of Biotechnology Program, Northwestern University, Evanston, IL, USA Correspondence: (*) Qian Chen and Mitsuyuki Matsumoto, as above. E-mails: qian.chen@us.astellas.com and mitsuyuki.matsumoto@us.astellas.com Article Note: (*) Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms Received 27 March 2012, revised 07 May 2012, accepted 08 May 2012
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titleSREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.(Report)
descriptionTo purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08180.x/abstract Byline: Qian Chen(1), Jeffrey H. Kogan(1), Adam K. Gross(1), Yuan Zhou(2), Noah M. Walton(1), Rick Shin(1), Carrie L. Heusner(1), Shinichi Miyake(1), Katsunori Tajinda(1), Kouichi Tamura(1), Mitsuyuki Matsumoto(1) Keywords: bromodeoxyuridine; cognition; dentate gyrus; mutant mouse; psychiatric disease Abstract SREB2/GPR85, a member of the super-conserved receptor expressed in brain (SREB) family, is the most conserved G-protein-coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over-expression) and knockout (KO, null-mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y-maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients. Author Affiliation: (1)CNS, Astellas Research Institute of America LLC, Skokie, IL 60077, USA (2)Master of Biotechnology Program, Northwestern University, Evanston, IL, USA Correspondence: (*) Qian Chen and Mitsuyuki Matsumoto, as above. E-mails: qian.chen@us.astellas.com and mitsuyuki.matsumoto@us.astellas.com Article Note: (*) Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms Received 27 March 2012, revised 07 May 2012, accepted 08 May 2012
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abstractTo purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2012.08180.x/abstract Byline: Qian Chen(1), Jeffrey H. Kogan(1), Adam K. Gross(1), Yuan Zhou(2), Noah M. Walton(1), Rick Shin(1), Carrie L. Heusner(1), Shinichi Miyake(1), Katsunori Tajinda(1), Kouichi Tamura(1), Mitsuyuki Matsumoto(1) Keywords: bromodeoxyuridine; cognition; dentate gyrus; mutant mouse; psychiatric disease Abstract SREB2/GPR85, a member of the super-conserved receptor expressed in brain (SREB) family, is the most conserved G-protein-coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over-expression) and knockout (KO, null-mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y-maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients. Author Affiliation: (1)CNS, Astellas Research Institute of America LLC, Skokie, IL 60077, USA (2)Master of Biotechnology Program, Northwestern University, Evanston, IL, USA Correspondence: (*) Qian Chen and Mitsuyuki Matsumoto, as above. E-mails: qian.chen@us.astellas.com and mitsuyuki.matsumoto@us.astellas.com Article Note: (*) Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms Received 27 March 2012, revised 07 May 2012, accepted 08 May 2012
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