Biochemical alteration in cerebrospinal fluid precedes behavioral deficits in Parkinsonian rats induced by 6-hydroxydopamine

Jia-Wei Lin MD, PhD , Chwen-Ming Shih PhD , Yen-Chou Chen PhD , Chien-Min Lin MD , Jo-Ting Tsai MD , Yung-Hsiao Chiang MD, PhD , Raymond Shih BS , Pei-Ling Chiu BS , Kuo-Sheng Hung MD, PhD , Yi-Shian Yeh MD , Li Wei MD , Wen-Ta Chiu MD, PhD , Liang-Yo Yang DVM, PhD
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引用次数: 1

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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6-羟多巴胺诱导的帕金森大鼠脑脊液生化改变先于行为缺陷
帕金森氏病是最常见的神经退行性运动障碍,影响65岁以上人口的至少1%。到目前为止,还没有证据表明脑脊液的生化变化发生在帕金森症状出现之前。在这项研究中,我们验证了帕金森动物脑脊液的生化变化先于行为缺陷的假设。方法双侧注入不同剂量的6-OHDA,观察1周后大鼠的运动行为、脑脊液生化变化及SNpc内多巴胺能神经元数量。结果SNpc多巴胺能神经元丢失超过70%的动物表现为行为迟缓和僵直,脑脊液HVA降低。相比之下,SNpc多巴胺能神经元丢失约42%的动物运动行为正常,但脑脊液HVA急剧下降。SNpc内多巴胺能神经元数量与脑脊液HVA水平呈正相关。结论6-OHDA诱导的帕金森大鼠SNpc中多巴胺能神经元数量与脑脊液中HVA水平呈正相关,脑脊液中生化改变先于行为缺陷。我们的研究结果强烈表明,需要进一步的研究来评估监测脑脊液中HVA水平对早期检测人类帕金森症状发作前SNpc中多巴胺能神经元丢失的有用性。
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Surgical Neurology
Surgical Neurology 医学-临床神经学
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