Lin Jia-Wei, Shih Chwen-Ming, Chen Yen-Chou, Lin Chien-Min, Tsai Jo-Ting, Chiang Yung-Hsiao, Shih Raymond, Chiu Pei-Ling, Hung Kuo-Sheng, Yeh Yi-Shian, Wei Li, Chiu Wen-Ta, Yang Liang-Yo
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110, Taiwan.
Surg Neurol. 2009 Dec;72 Suppl 2:S55-65; discussion S65. doi: 10.1016/j.wneu.2009.09.005.
Parkinson's disease, affecting at least 1% of population older than 65 years, is the most common neurodegenerative movement disorder. Up to now, no evidence has demonstrated that biochemical changes in CSF occur preceding the onset of Parkinson's symptoms. In this study, we tested the hypothesis that biochemical changes in CSF precede behavioral deficits in Parkinsonian animals.
We infused different doses of 6-OHDA into the MFB of rats bilaterally and examined the animals' movement behaviors, biochemical alterations in CSF, and dopaminergic neuronal number in the SNpc 1 week later.
Our results indicated that animals with over 70% dopaminergic neuronal loss in the SNpc exhibited behavioral bradykinesia and rigidity, and a decrease of HVA in CSF. In contrast, animals with about 42% dopaminergic neuronal loss in the SNpc showed normal movement behaviors, but displayed a drastic decline of HVA in CSF. Furthermore, the number of dopaminergic neurons in the SNpc was positively correlated with the HVA level in CSF.
Our findings demonstrate that biochemical alteration in CSF foreruns behavioral deficits and the HVA level in CSF is positively correlated with the number of dopaminergic neurons in the SNpc of Parkinsonian rats induced by 6-OHDA. Our results strongly suggest that additional studies are needed to evaluate usefulness of monitoring the HVA level in CSF for early detection of the loss of dopaminergic neurons in the SNpc that precedes the onset of Parkinsonian symptoms in humans.
帕金森病是最常见的神经退行性运动障碍，影响着至少1%的65岁以上人群。到目前为止，尚无证据表明脑脊液中的生化变化在帕金森病症状出现之前就已发生。在本研究中，我们检验了脑脊液生化变化先于帕金森病动物行为缺陷出现的假说。
我们双侧向大鼠的内侧前脑束注入不同剂量的6-羟基多巴胺，并在1周后检查动物的运动行为、脑脊液中的生化改变以及黑质致密部多巴胺能神经元数量。
我们的结果表明，黑质致密部多巴胺能神经元损失超过70%的动物表现出行为迟缓及僵硬，脑脊液中高香草酸水平降低。相比之下，黑质致密部多巴胺能神经元损失约42%的动物运动行为正常，但脑脊液中高香草酸水平急剧下降。此外，黑质致密部多巴胺能神经元数量与脑脊液中高香草酸水平呈正相关。
我们的研究结果表明，脑脊液中的生化改变先于行为缺陷出现，且脑脊液中高香草酸水平与6-羟基多巴胺诱导的帕金森病大鼠黑质致密部多巴胺能神经元数量呈正相关。我们的结果强烈提示，需要进一步研究以评估监测脑脊液中高香草酸水平对早期检测人类帕金森病症状出现之前黑质致密部多巴胺能神经元损失的有用性。
