Korotkova Tatiana M, Ponomarenko Alexei A, Haas Helmut L, Sergeeva Olga A
Institute of Neurophysiology, Heinrich-Heine-University, Physiology II, POB 101007, Duesseldorf, Germany.
Eur J Neurosci. 2005 Sep;22(6):1287-93. doi: 10.1111/j.1460-9568.2005.04327.x.
The transcription factor Pitx3 is expressed selectively in the midbrain and regulates the differentiation and survival of dopaminergic neurons. Lack of this factor results in a degeneration similar to that seen in Parkinson's disease. We have studied the pattern and the level of expression of Pitx3 in dopaminergic neurons of 3- to 4-week-old Wistar rats. We report Pitx3 expression in almost all dopaminergic substantia nigra (SN) and ventral tegmental area (VTA) neurons. It is coexpressed with the neuroprotective marker calbindin (CB) in a larger population of VTA (43%) than SN (16%) dopaminergic neurons. The level of Pitx3 mRNA, determined by semiquantitative RT-PCR, is approximately 6x higher in VTA than in SN single neurons. In the VTA but not in SN the level of Pitx3 is associated with the presence of CB: in CB-positive neurons the expression of Pitx3 mRNA is 3.6x higher than in CB-negative cells. CB is expressed in a larger population of VTA than SN neurons and the relative level of CB expression is 4x higher in VTA than in SN. A higher Pitx3 expression level and higher coexpression of Pitx3 and CB in VTA than in SN neurons may contribute to the different vulnerability of these dopaminergic nuclei to neurodegeneration.
转录因子Pitx3在中脑选择性表达，调控多巴胺能神经元的分化和存活。缺乏该因子会导致类似于帕金森病所见的退化。我们研究了3至4周龄Wistar大鼠多巴胺能神经元中Pitx3的表达模式和水平。我们报道Pitx3在几乎所有多巴胺能黑质（SN）和腹侧被盖区（VTA）神经元中表达。在VTA多巴胺能神经元群体（43%）中，它与神经保护标志物钙结合蛋白（CB）共表达的比例高于SN多巴胺能神经元群体（16%）。通过半定量RT-PCR测定，Pitx3 mRNA水平在VTA单个神经元中比在SN中约高6倍。在VTA而非SN中，Pitx3水平与CB的存在相关：在CB阳性神经元中，Pitx3 mRNA表达比在CB阴性细胞中高3.6倍。CB在VTA神经元群体中的表达比例高于SN，且CB表达的相对水平在VTA中比在SN中高4倍。与SN神经元相比，VTA中更高的Pitx3表达水平以及Pitx3与CB更高的共表达可能导致这些多巴胺能核团对神经退行性变的易感性不同。
