Cave John W, Baker Harriet
Department of Neurology and Neuroscience, Weill Cornell Medical College, Burke Medical Research Institute, White Plains, NY 10606, USA.
Adv Exp Med Biol. 2009;651:15-35. doi: 10.1007/978-1-4419-0322-8_2.
The brain contains a number of distinct regions that share expression ofdopamine (DA) and its requisite biosynthetic machinery, but otherwise encompass a diverse array of features and functions. Across the vertebrate family, the olfactory bulb (OB) contains the major DA system in the forebrain. OB DA cells are primarily periglomerular interneurons that define the glomerular structures in which they receive innervation from olfactory receptor neurons as well as mitral and tufted cells, the primary OB output neurons. The OB DA cells are necessary for both discrimination and the dynamic range over which odorant sensory information can be detected. In the embryo, OB DA neurons are derived from the ventricular area of the evaginating telencephalon, the dorsal lateral ganglionic eminence and the septum. However, most OB DA interneurons are generated postnatally and continue to be produced throughout adult life from neural stem cells in the subventricular zone of the lateral ventricle and rostral migratory stream. Adult born OB DA neurons are capable of integrating into existing circuits and do not appear to degenerate in Parkinson's disease. Several genes have been identified that regulate the differentiation of OB DA interneurons from neural stem cells. These include transcription factors that modify the expression of tyrosine hydroxylase, the first enzyme in the DA biosynthetic pathway and a reliable marker of the DA phenotype. Elucidation of the molecular genetic pathways of OB DA differentiation may advance the development of strategies to treat neurological disease.
大脑包含许多不同的区域，这些区域共享多巴胺（DA）及其必需的生物合成机制的表达，但在其他方面具有各种各样的特征和功能。在整个脊椎动物家族中，嗅球（OB）包含前脑中主要的DA系统。OB DA细胞主要是球周中间神经元，它们定义了肾小球结构，在这些结构中，它们从嗅觉受体神经元以及OB主要输出神经元——二尖瓣细胞和簇状细胞接收神经支配。OB DA细胞对于辨别以及检测气味感觉信息的动态范围都是必需的。在胚胎中，OB DA神经元源自外翻端脑的脑室区域、背外侧神经节隆起和隔膜。然而，大多数OB DA中间神经元是在出生后产生的，并且在成年期从侧脑室室下区和吻侧迁移流中的神经干细胞持续产生。成年新生的OB DA神经元能够整合到现有回路中，并且在帕金森病中似乎不会退化。已经鉴定出几个调节神经干细胞分化为OB DA中间神经元的基因。这些基因包括修饰酪氨酸羟化酶表达的转录因子，酪氨酸羟化酶是DA生物合成途径中的第一种酶，也是DA表型的可靠标志物。阐明OB DA分化的分子遗传途径可能会推动治疗神经疾病策略的发展。
