Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea.
Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea.
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1211-8. doi: 10.1016/j.bbrc.2014.03.085. Epub 2014 Mar 26.
Midbrain dopaminergic (DA) neurons are involved in the regulation of voluntary movement and in emotion-related behaviors and are affected in Parkinson's disease (PD). The homeodomain transcription factor Pitx3, which is uniquely expressed in midbrain DA neurons, plays a critical role in the development, function and maintenance of midbrain DA neurons. Pitx3 deficiency results in selective deficits of midbrain DA neurons in the substantia nigra pars compacta (SNc), reminiscent of the specific DA neuronal loss observed in PD. In this study, we found that selective overexpression of Pitx3 in intact midbrain DA neurons significantly affects the function of midbrain DA neurons. We observed changes in DA levels and gene expressions in mice overexpressing Pitx3. Furthermore, motor coordination and locomotion activities are significantly affected in mice overexpressing Pitx3, suggesting that the expression level of Pitx3 plays an important role in the function of midbrain DA neuron in vivo.
中脑多巴胺（DA）神经元参与调节自主运动和与情绪相关的行为，并在帕金森病（PD）中受到影响。同源域转录因子 Pitx3 特异性表达于中脑 DA 神经元，在中脑 DA 神经元的发育、功能和维持中发挥关键作用。Pitx3 缺失导致黑质致密部（SNc）中中脑 DA 神经元的选择性缺失，类似于 PD 中观察到的特定 DA 神经元缺失。在这项研究中，我们发现中脑 DA 神经元中 Pitx3 的选择性过表达显著影响中脑 DA 神经元的功能。我们观察到过表达 Pitx3 的小鼠中 DA 水平和基因表达的变化。此外，过表达 Pitx3 的小鼠的运动协调和运动活动明显受到影响，这表明 Pitx3 的表达水平在体内中脑 DA 神经元的功能中发挥重要作用。
