| 1 | Curr. Med. Chem. 2003 May 10: 857-70 |
|---|
| PMID | 12678688 |
| Title | The control of dopamine neuron development, function and survival: insights from transgenic mice and the relevance to human disease. |
| Abstract | Transgenic technology, especially the use of homologous recombination to disrupt specific genes to produce knockout mice, has added considerably to the understanding of dopamine (DA) neuron develop, survival and function. The current review summarizes results from knockout mice with the target disruption of genes involved in the development of DA neurons (engrailed 1 and 2, LMX1B, and Nurr1), in maintaining DA neurotransmission (tyrosine hydroxylase, vesicular monoamine transporter, DA transporter, DA D2 and D3 receptors) and important for DA neuron survival (alpha-synuclein, glia cell line-derived neurotrophic factor and superoxide dismutase). As alterations in DA neurotransmission have been implicated in a number of human neuropathologies including Parkinson's disease, schizophrenia and attention deficit/hyperactivity disorder, understanding how specific genes are involved in the function of DA neurons and the compensatory changes that result from loss or reduction in gene expression could provide important insight for the treatment of these diseases. |
| SCZ Keywords | schizophrenia |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2010 Aug 34: 1094-7 |
|---|
| PMID | 20570600 |
| Title | Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia. |
| Abstract | The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented. |
| SCZ Keywords | schizophrenia |
| 3 | Neurosci. Lett. 2010 Dec 486: 220-3 |
|---|
| PMID | 20884326 |
| Title | Maternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon. |
| Abstract | schizophrenia is a neurodevelopment disorder that is strongly associated with alterations in dopamine neurotransmission. Common features of animal models of schizophrenia include behavioural, cognitive and/or pharmacological abnormalities reflective of aberrant DA signaling. The aim of this study was to examine the expression of genes important for dopaminergic development and maturation within the embryonic mesencephalon using an epidemiologically-informed animal model of schizophrenia, the developmental vitamin D (DVD) deficient rat model. Two groups of female Sprague-Dawley rats were fed either a diet replete (1000IU/kg) or deplete (0IU/kg) of vitamin D, mated and foetal mesencephalon collected at embryonic day (E) E12 or E15. Using real time-PCR, the DVD-deficient embryos had a significant reduction in factors crucial in specifying dopaminergic phenotype, such as Nurr1 and p57Kip2. No group differences were found for LMX1B or Ptx3. Reductions in these specification factors may alter the ontogeny of DA neurons and may ultimately help to explain the behavioural abnormalities reported in adult offspring from this model. |
| SCZ Keywords | schizophrenia |