Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

Kesby, James P., Cui, Xiaoying, Burne, Thomas H. J. and Eyles, Darryl W. (2013) Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia. Frontiers in Cellular Neuroscience, 7 111: 1-13. doi:10.3389/fncel.2013.00111

Author Kesby, James P.
Cui, Xiaoying
Burne, Thomas H. J.
Eyles, Darryl W.
Title Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia
Journal name Frontiers in Cellular Neuroscience   Check publisher's open access policy
ISSN 1662-5102
Publication date 2013-07-17
Sub-type Critical review of research, literature review, critical commentary
DOI 10.3389/fncel.2013.00111
Open Access Status DOI
Volume 7
Issue 111
Start page 1
End page 13
Total pages 13
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2014
Language eng
Formatted abstract
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.
Keyword Amphetamine
Orphan nuclear receptor
Prenatal immune activation
Tyrosine-hydroxylase gene
D DVD deficiency
Neurotrophic factor
Synthesis capacity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2014 Collection
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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