INSERM U 643, CHU Hôtel Dieu, 30 boulevard Jean Monnet, 44093 Nantes cedex 1, France.
Parkinsons Dis. 2011;2011:987084. doi: 10.4061/2011/987084. Epub 2011 Jun 28.
A transgenic Sprague Dawley rat bearing the A30P and A53T α-synuclein (α-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human α-syn mutations on the neuropathological events involved in the progression of the Parkinson's disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated α-syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human α-syn co-localized in TH-positive OB neurons. No human α-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated α-syn on the development of olfactory deficits.
为了更好地了解人类α-突触核蛋白突变在帕金森病（PD）进展相关神经病理事件中的作用，我们构建了一种在酪氨酸羟化酶启动子控制下携带 A30P 和 A53T α-突触核蛋白（α-syn）人类突变的转基因 Sprague Dawley 大鼠。该大鼠在没有运动障碍的情况下表现出嗅觉缺陷，如大多数早期 PD 病例中观察到的那样。为了研究突变的α-syn 对细胞增殖的作用，我们重点研究了侧脑室下区（SVZ）和嗅球（OB），因为增殖的变化可能会影响 OB 功能。我们还研究了其对 OB 多巴胺能神经支配的影响。人类α-syn 与 TH 阳性 OB 神经元共定位。SVZ 中未观察到人类α-syn。观察到 OB 肾小球层而非颗粒层以及 SVZ 中常驻细胞增殖显著增加。TH 神经支配在肾小球层内显著增加，而肾小球大小没有增加。我们的大鼠可能是研究人类突变α-syn 对嗅觉缺陷发展作用的良好模型。
