Joyce J N, Smutzer G, Whitty C J, Myers A, Bannon M J
Thomas H. Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona, USA.
Mov Disord. 1997 Nov;12(6):885-97. doi: 10.1002/mds.870120609.
The molecular characteristics of midbrain dopamine (DA) neurons have been extensively studied in Parkinson's disease (PD). No such studies of the characteristics of midbrain DA neurons in Alzheimer's disease (AD) or Alzheimer's disease with parkinsonism (AD/Park) have been published. We examined the levels of tyrosine hydroxylase (TH) protein, and the expression of TH and dopamine transporter (DAT) mRNAs, in midbrain neurons of PD, AD, and AD/Park cases. In PD, the loss of TH protein in the ventral tier of the substantia nigra pars compacta (SNpc) of the PD group in accompanied by severe losses in the number of neurons that express TH mRNA and DAT mRNA (74% loss). Remaining neurons show a shift to higher concentrations of TH mRNA but a shift to lower concentrations of DAT mRNA per cell. Hence, there is evidence that compensation in the remaining neurons can elevate concentrations of TH mRNA and lower DAT mRNA. Alternatively, there may be a predilection for a loss of neurons with high levels of DAT mRNA and low TH mRNA levels within the SNpc of PD cases. There was no change in TH protein but an elevation of TH mRNA concentrations per neuron without any change in concentrations of DAT mRNA in the AD group. The AD/Park group did not exhibit changes in the level of TH protein, but showed a small loss (26%) of neurons in the SNpc and a greater loss in other regions of the midbrain (43-53%). Remaining DA neurons showed a marked shift to lower concentrations of DAT mRNA per neuron and a nonsignificant shift in cellular concentration of TH mRNA to higher levels. This is consistent with our previous work showing that with AD/Park there is a significant reduction in the number of DAT sites located on DA terminals in the striatum, but the midbrain neurons have not died. Our results indicate that the differential regulation of mRNAs encoding TH and DAT is similar in the parkinsonian disorders (PD and AD/Park) even though the degree of cell death is very different. This might suggest that compensatory events occur in these DA neurons in AD/Park that are similar to those in PD and that result in differential effects on mRNAs encoding TH and DAT proteins.
帕金森病（PD）中脑多巴胺（DA）神经元的分子特征已得到广泛研究。目前尚无关于阿尔茨海默病（AD）或帕金森叠加型阿尔茨海默病（AD/Park）中脑DA神经元特征的此类研究发表。我们检测了PD、AD和AD/Park病例中脑神经元中酪氨酸羟化酶（TH）蛋白水平以及TH和多巴胺转运体（DAT）mRNA的表达。在PD中，PD组黑质致密部（SNpc）腹侧层TH蛋白的缺失伴随着表达TH mRNA和DAT mRNA的神经元数量的严重减少（减少74%）。剩余神经元显示TH mRNA浓度向更高水平转变，但每个细胞的DAT mRNA浓度向更低水平转变。因此，有证据表明剩余神经元中的代偿可提高TH mRNA浓度并降低DAT mRNA浓度。或者，PD病例的SNpc中可能存在对高DAT mRNA水平和低TH mRNA水平神经元丢失的偏好。AD组TH蛋白无变化，但每个神经元的TH mRNA浓度升高，而DAT mRNA浓度无任何变化。AD/Park组TH蛋白水平无变化，但SNpc中神经元有少量丢失（26%），中脑其他区域丢失更多（43 - 53%）。剩余的DA神经元显示每个神经元的DAT mRNA浓度明显向更低水平转变，而细胞内TH mRNA浓度向更高水平的转变不显著。这与我们之前的研究结果一致，即AD/Park时纹状体DA终末上DAT位点的数量显著减少，但中脑神经元未死亡。我们的结果表明，尽管细胞死亡程度差异很大，但帕金森病（PD和AD/Park）中编码TH和DAT的mRNA的差异调节是相似的。这可能表明AD/Park的这些DA神经元中发生了与PD中相似的代偿事件，并对编码TH和DAT蛋白的mRNA产生不同影响。
