Zetterström R H, Williams R, Perlmann T, Olson L
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Brain Res Mol Brain Res. 1996 Sep 5;41(1-2):111-20. doi: 10.1016/0169-328x(96)00074-5.
Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid hormone receptor family involved in immediate early responses to stimuli such as growth factors. In-situ hybridization in the developing and adult mouse and rat demonstrated Nurr1 mRNA in several regions during early central nervous system (CNS) development. Expression persisted through the pre- and postnatal periods and was also found in several areas in the adult CNS. Positive areas include the olfactory bulb, parts of the cortex, the hippocampal formation and substantia nigra where Nurr1 and tyrosine hydroxylase mRNAs were co-expressed. 6-Hydroxydopamine-induced degeneration of mesencephalic dopamine neurons led to a corresponding loss of Nurr1 mRNA, demonstrating a link between Nurr1 and dopaminergic neurons. NGFI-B mRNA was not found in the prenatal CNS but was highly expressed in the adult brain in many areas including the olfactory bulb, cortex, basal ganglia and hippocampus. The spatiotemporal distribution of Nurr1 and NGFI-B mRNAs suggests that these transcription factors are involved in the development and maturation of specific sets of CNS neurons. The experimental data imply that one of these functions may be to control gene regulatory events important for development and function of those neurons that degenerate in patients with Parkinson's disease.
Nurr1和NGFI-B是类固醇-甲状腺激素受体家族中密切相关的孤儿成员，参与对生长因子等刺激的早期即时反应。在发育中和成年小鼠及大鼠中进行的原位杂交显示，在中枢神经系统（CNS）早期发育过程中，Nurr1 mRNA存在于多个区域。其表达在出生前和出生后阶段持续存在，在成年CNS的多个区域也有发现。阳性区域包括嗅球、部分皮质、海马结构和黑质，其中Nurr1和酪氨酸羟化酶mRNA共同表达。6-羟基多巴胺诱导的中脑多巴胺神经元变性导致Nurr1 mRNA相应减少，表明Nurr1与多巴胺能神经元之间存在联系。在产前CNS中未发现NGFI-B mRNA，但在成年大脑的许多区域高度表达，包括嗅球、皮质、基底神经节和海马体。Nurr1和NGFI-B mRNA的时空分布表明，这些转录因子参与了特定中枢神经系统神经元组的发育和成熟。实验数据表明，这些功能之一可能是控制对帕金森病患者中退化的神经元的发育和功能至关重要的基因调控事件。
