DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats

Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have sh...

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Autores principales: Lee, Heekyung, Kang, Eunchai, GoodSmith, Douglas, Yoon, Do Yeon, Song, Hongjun, Knierim, James J., Ming, Guo-li, Christian, Kimberly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479724/
https://www.ncbi.nlm.nih.gov/pubmed/26161071
http://dx.doi.org/10.3389/fnsys.2015.00093
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author Lee, Heekyung
Kang, Eunchai
GoodSmith, Douglas
Yoon, Do Yeon
Song, Hongjun
Knierim, James J.
Ming, Guo-li
Christian, Kimberly M.
author_facet Lee, Heekyung
Kang, Eunchai
GoodSmith, Douglas
Yoon, Do Yeon
Song, Hongjun
Knierim, James J.
Ming, Guo-li
Christian, Kimberly M.
author_sort Lee, Heekyung
collection PubMed
description Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function.
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spelling pubmed-44797242015-07-09 DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats Lee, Heekyung Kang, Eunchai GoodSmith, Douglas Yoon, Do Yeon Song, Hongjun Knierim, James J. Ming, Guo-li Christian, Kimberly M. Front Syst Neurosci Neuroscience Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. Frontiers Media S.A. 2015-06-25 /pmc/articles/PMC4479724/ /pubmed/26161071 http://dx.doi.org/10.3389/fnsys.2015.00093 Text en Copyright © 2015 Lee, Kang, GoodSmith, Yoon, Song, Knierim, Ming and Christian. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lee, Heekyung
Kang, Eunchai
GoodSmith, Douglas
Yoon, Do Yeon
Song, Hongjun
Knierim, James J.
Ming, Guo-li
Christian, Kimberly M.
DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title_full DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title_fullStr DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title_full_unstemmed DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title_short DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats
title_sort disc1-mediated dysregulation of adult hippocampal neurogenesis in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479724/
https://www.ncbi.nlm.nih.gov/pubmed/26161071
http://dx.doi.org/10.3389/fnsys.2015.00093
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