期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2013.00111
关键词
amphetamine; MK-801; dopamine; behavior; differentiation; development
资金
- Queensland Health
- National Health and Medical Research Council
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 an neuro developmental 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 neuro developmental 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 analtered behavioral profilein response to DA releasing and blocking agents that are reminiscent of that see nin schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. Inparticular, 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 neuronontogeny to induce the behavior al abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are presenting people who develop schizophrenia prior to on set 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 to get here evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据