Arnauld E, Arsaut J, Tafani J A, Demotes-Mainard J
INSERM U-394, Bordeaux, France.
Brain Res Mol Brain Res. 1995 Jun;30(2):223-32. doi: 10.1016/0169-328x(95)00011-g.
During striatal development, dopamine afferents initially reach the striosomal compartment, and this early dopamine innervation is thought to influence, through the D1 receptors first expressed in the developing patches, the phenotype of target striatal cells. Dopaminergic control of gene expression during ontogeny could be mediated by transcription factors such as c-fos, whose expression is regulated by synaptic signals. However, in the striatum of intact adult animals, D1 dopamine agonists fail to induce c-fos expression. The c-fos response to D1 receptor activation in adults requires a previous sensitization of dopaminergic receptors by chronic treatment with reserpine or by lesion of the nigro-striatal pathway. In this work, we investigated through in situ hybridization the ability of striatal cells to express c-fos messenger RNA (mRNA) in response to the D1 agonist SKF 38393 (4 to 8 mg/kg) in developing mice. During a transient postnatal period, c-fos expression in a patchy distribution was induced by D1 receptor activation: only a faint response was detected on postnatal day 1, but islands of strong hybridization signals for c-fos mRNA in response to the D1 agonist were observed at postnatal day 3, with a progressive decrease in intensity from day 6 to day 15. The distribution of this transient c-fos response corresponded to the early striosomal compartment since it matched with the regions of intense mu-opioid and dopamine-D1 receptor binding, as assessed by autoradiography performed on adjacent sections. By day 21, as in adult animals, no more c-fos response to D1 agonists was observed, except in the most caudal division of the striatum. Strong expression, which persisted into adulthood, was detected in this region from the third postnatal day. This induction of striatal c-fos expression by D1 agonists during early postnatal development is indicative of an enhanced sensitivity of D1 receptors or of D1-associated transduction pathways compared to the adult pattern, and suggests a possible role for dopamine-controlled c-fos gene expression in the development of target striatal neurons during this critical period.
在纹状体发育过程中，多巴胺传入纤维最初到达纹状小体区，这种早期的多巴胺神经支配被认为通过发育中的斑块中最早表达的D1受体影响目标纹状体细胞的表型。个体发育过程中基因表达的多巴胺能控制可能由转录因子如c-fos介导，其表达受突触信号调节。然而，在完整成年动物的纹状体中，D1多巴胺激动剂不能诱导c-fos表达。成年动物中对D1受体激活的c-fos反应需要事先通过利血平慢性治疗或黑质-纹状体通路损伤使多巴胺能受体致敏。在这项研究中，我们通过原位杂交研究了发育中小鼠纹状体细胞对D1激动剂SKF 38393（4至8 mg/kg）产生反应而表达c-fos信使核糖核酸（mRNA）的能力。在出生后的一个短暂时期内，D1受体激活诱导了呈斑片状分布的c-fos表达：出生第1天仅检测到微弱反应，但在出生第3天观察到对D1激动剂有强烈杂交信号的c-fos mRNA岛，从第6天到第15天强度逐渐降低。这种短暂的c-fos反应的分布与早期纹状小体区相对应，因为它与通过对相邻切片进行放射自显影评估的强μ-阿片样物质和多巴胺-D1受体结合区域相匹配。到第21天，与成年动物一样，除了纹状体最尾端部分外，未观察到对D1激动剂的c-fos反应。从出生后第3天起，在该区域检测到持续到成年的强表达。出生后早期发育过程中D1激动剂对纹状体c-fos表达的这种诱导表明与成年模式相比，D1受体或与D1相关的转导途径的敏感性增强，并提示在这个关键时期多巴胺控制的c-fos基因表达在目标纹状体神经元发育中可能发挥作用。
