Nakatani Noriaki, Yoshikawa Takeo
Laboratory for Molecular Psychiatry, Brain Science Institute, 2-1 Hirosawa, Wako, 351-0198 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2003 Aug;23(4):161-9.
The pathophysiology of psychiatric diseases including depression is characterized by the involvement of many genes contributing a small effect. This genetic complexity means larger amounts of information can be gathered by studying the disease process as a single entity, in an animal model. A number of genetically modified animals showing both depressive and anti-depressive phenotypes have been generated. Approximately ten of these models are in current use for screening novel antidepressants. The development of new therapies is intimately linked to the elucidation of mechanisms via which the drugs work and therefore the mechanisms of disease. It is now possible to combine the information from animal models with sophisticated technology including DNA microarray analysis. In this setting, the animal models can provide information about genes altered in both the depressive state and after anti-depressive treatment, whilst DNA microarrays can identify these genes, as well as the direction of change. This information will eventually lead to the discovery of new mechanisms involved in disease pathology. Here we summarize approaches for identifying genes related to depression.
包括抑郁症在内的精神疾病的病理生理学特征是涉及许多基因,每个基因的作用较小。这种遗传复杂性意味着通过在动物模型中将疾病过程作为一个整体来研究,可以收集到更多信息。已经培育出了许多表现出抑郁和抗抑郁表型的转基因动物。目前大约有十种这样的模型用于筛选新型抗抑郁药。新疗法的开发与阐明药物作用机制以及疾病机制密切相关。现在可以将动物模型的信息与包括DNA微阵列分析在内的先进技术相结合。在这种情况下,动物模型可以提供有关抑郁状态和抗抑郁治疗后改变的基因的信息,而DNA微阵列可以识别这些基因以及变化方向。这些信息最终将导致发现疾病病理中涉及的新机制。在此我们总结了识别与抑郁症相关基因的方法。