Galter Dagmar, Westerlund Marie, Belin Andrea Carmine, Olson Lars
Karolinska Institutet, Department of Neuroscience, Retzius väg 8 B2:4, S-171 77 Stockholm, Sweden.
Physiol Behav. 2007 Sep 10;92(1-2):46-53. doi: 10.1016/j.physbeh.2007.05.046. Epub 2007 May 23.
DJ-1 (PARK7) has been implicated in early onset and familial cases of Parkinson's disease (PD). We therefore mapped cellular activity patterns of the DJ-1 gene in human and rodent brain tissue with radioactive in-situ hybridization. In all three mammals mRNA expression was restricted mainly to neurons in all regions analyzed. White matter, such as crus cerebri and capsula interna appeared negative, suggesting that glial cells express DJ-1 at levels below the detection limit of our method. We compared DJ-1 mRNA expression to the neuronal marker UCH-L1, which has also been implicated in PD, and found lower levels for DJ-1 but very similar patterns of expression. Measurement of the signal intensity revealed that human frontal cortex of control cases expressed DJ-1 mRNA more abundantly than other regions such as substantia nigra in the midbrain. Comparing DJ-1 expression in dopamine neurons on hemi-sections from controls and patients we could not detect any difference between 14 controls, 8 idiopathic Parkinson and 5 schizophrenia cases. Of note, DJ-1 is expressed in several other tissues such as the liver, gastrointestinal tract, adrenal and pituitary gland and during embryonic development, while UCH-L1 has a strictly neuronal expression also outside the CNS. We conclude that DJ-1 and UCH-L1, like other genes linked to PD, are not expressed specifically in DA neurons, but instead generally in neurons. The abundant expression of DJ-1 in certain peripheral tissues and of UCH-L1 in peripheral neurons may also be of relevance for the spectrum of symptoms in different forms of PD.
DJ-1(PARK7)与帕金森病(PD)的早发性和家族性病例有关。因此,我们用放射性原位杂交技术绘制了DJ-1基因在人和啮齿动物脑组织中的细胞活性模式。在所有三种哺乳动物中,mRNA表达主要局限于所有分析区域的神经元。白质,如大脑脚和内囊呈阴性,这表明胶质细胞表达DJ-1的水平低于我们方法的检测限。我们将DJ-1 mRNA表达与同样与PD有关的神经元标记物UCH-L1进行比较,发现DJ-1水平较低,但表达模式非常相似。信号强度测量显示,对照病例的人类额叶皮质比中脑黑质等其他区域更丰富地表达DJ-1 mRNA。比较对照组和患者半脑切片中多巴胺神经元的DJ-1表达,我们在14名对照者、8名特发性帕金森病患者和5名精神分裂症患者之间未检测到任何差异。值得注意的是,DJ-1在肝脏、胃肠道、肾上腺和垂体等其他几种组织中以及胚胎发育过程中表达,而UCH-L1在中枢神经系统之外也有严格的神经元表达。我们得出结论,DJ-1和UCH-L1与其他与PD相关的基因一样,并非特异性地在多巴胺能神经元中表达,而是普遍在神经元中表达。DJ-1在某些外周组织中的丰富表达以及UCH-L1在外周神经元中的表达也可能与不同形式PD的症状谱相关。