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Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia
Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is consi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713405/ https://www.ncbi.nlm.nih.gov/pubmed/23882183 http://dx.doi.org/10.3389/fncel.2013.00111 |
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author | Kesby, James P. Cui, Xiaoying Burne, Thomas H. J. Eyles, Darryl W. |
author_facet | Kesby, James P. Cui, Xiaoying Burne, Thomas H. J. Eyles, Darryl W. |
author_sort | Kesby, James P. |
collection | PubMed |
description | Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology. |
format | Online Article Text |
id | pubmed-3713405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37134052013-07-23 Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia Kesby, James P. Cui, Xiaoying Burne, Thomas H. J. Eyles, Darryl W. Front Cell Neurosci Neuroscience Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology. Frontiers Media S.A. 2013-07-17 /pmc/articles/PMC3713405/ /pubmed/23882183 http://dx.doi.org/10.3389/fncel.2013.00111 Text en Copyright © Kesby, Cui, Burne and Eyles. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Neuroscience Kesby, James P. Cui, Xiaoying Burne, Thomas H. J. Eyles, Darryl W. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title | Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title_full | Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title_fullStr | Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title_full_unstemmed | Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title_short | Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia |
title_sort | altered dopamine ontogeny in the developmentally vitamin d deficient rat and its relevance to schizophrenia |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713405/ https://www.ncbi.nlm.nih.gov/pubmed/23882183 http://dx.doi.org/10.3389/fncel.2013.00111 |
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