Crispino M, Tocco G, Feldman J D, Herschman H R, Baudry M
Neuroscience Program, Hedco Neuroscience Building, Room 311, University of Southern California, Los Angeles, CA 90089-2520, USA.
Brain Res Mol Brain Res. 1998 Aug 31;59(2):178-88. doi: 10.1016/s0169-328x(98)00143-0.
Nurr1 is an immediate early gene encoding a member of the steroid-thyroid hormone receptor family. In PC12 cells, Nurr1 is readily induced by membrane depolarization, but not by growth factors. Nurr1 is predominantly expressed in the brain, and is essential to the differentiation of midbrain dopaminergic neurons. However, Nurr1 is also expressed in brain regions unrelated to dopaminergic neurons, e.g., hippocampus and cerebral cortex, and its immediate induction following seizure activity suggests a potential involvement of this transcription factor in modulating gene expression in the nervous system. To investigate the response of Nurr1 to neuronal activation, we analyzed Nurr1 mRNA expression in neonatal and adult rat brain following kainic acid (KA)-induced seizure. In P7 animals, systemic injection of KA increased Nurr1 mRNA levels in a few hilar cells of the dentate gyrus and some pyramidal cells of the CA3 region of the hippocampus. In older animals, Nurr1 induction progressively expanded to all hippocampal regions (P14, P21) and eventually to cortical regions (adult). The increase was rapid and transient in the dentate gyrus, a structure resistant to the neurotoxic effect of KA, and was more prolonged in other regions more susceptible to KA toxicity. Induction of Nurr1 at early postnatal stages and rapid increase in the dentate gyrus following KA-induced seizure, suggest that Nurr1 expression is modulated by neuronal activity. On the other hand, prolonged Nurr1 induction in regions sensitive to KA toxicity indicates a possible involvement of Nurr1 in selective neuronal vulnerability.
Nurr1是一种即刻早期基因，编码类固醇 - 甲状腺激素受体家族的一个成员。在PC12细胞中，Nurr1很容易被膜去极化诱导，但不能被生长因子诱导。Nurr1主要在大脑中表达，对中脑多巴胺能神经元的分化至关重要。然而，Nurr1也在与多巴胺能神经元无关的脑区表达，例如海马体和大脑皮层，并且其在癫痫活动后的即刻诱导表明该转录因子可能参与调节神经系统中的基因表达。为了研究Nurr1对神经元激活的反应，我们分析了海藻酸（KA）诱导癫痫发作后新生和成年大鼠脑中Nurr1 mRNA的表达。在P7动物中，全身注射KA可增加齿状回的一些门区细胞和海马体CA3区的一些锥体细胞中的Nurr1 mRNA水平。在年龄较大的动物中，Nurr1的诱导逐渐扩展到所有海马区（P14、P21），最终扩展到皮质区（成年）。在对KA神经毒性作用具有抗性的齿状回中，这种增加是快速且短暂的，而在其他对KA毒性更敏感的区域中则持续时间更长。出生后早期阶段Nurr1的诱导以及KA诱导癫痫发作后齿状回中Nurr1的快速增加，表明Nurr1的表达受神经元活动调节。另一方面，在对KA毒性敏感的区域中Nurr1的诱导持续时间延长，表明Nurr1可能参与选择性神经元易损性。
