Maniyath Sukala Puthuparambil, Solaiappan Narayanan, Rathinasamy Muthusamy
Associate Professor, Department of Anatomy, Perundurai Medical College, Erode, Tamil Nadu, India.
Retired Professor, Department of Anatomy, Perundurai Medical College, Erode, Tamil Nadu, India.
J Clin Diagn Res. 2017 Mar;11(3):AF01-AF05. doi: 10.7860/JCDR/2017/24955.9604. Epub 2017 Mar 1.
Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study.
To assess all the motor deficits in lesioned animals that are due to the depletion of dopaminergic neurons or its terminals, the lesioned animals were administered with anti-parkinsonian drug, Levodopa which should counteract motor deficits in rats.
The unilateral partially lesioned PD model was induced by rotenone stereotaxically into two sites of striatum of male Wistar albino rats at a dosage of 25 μg of rotenone/site. Rats were tested for its neurobehavioural activity on 7 day, 14 day, 21 day and on 30 day after rotenone infusion and compared with the sham group and sacrificed on 21 and 30 day for microscopic studies. L-DOPA was administered from 21 day to 30 day after lesion and compared with the lesioned group for the motor performance and sacrificed on 30 day for histology. Statistical analysis using One-way Analysis of variance followed by Tukey's test was applied for behavioural studies.
Statistical analysis showed that the signs and symptoms like motor in-coordination and postural disturbances are highly significant (p<0.05) on 14 and 21 day after administration of rotenone when compared to sham group. In L-DOPA treated rats, all the motor deficits were reversed. The neuronal cell death was minimal and sprouting of nerve terminals was detected. In lesioned group, the degeneration of nerve terminals and striatal neurons were in progressive manner.
These findings suggest that intrastriatal infusion of rotenone at a moderate dose could be used for producing hemiparkinsonian partially lesioned animal model without any mortality. Hence, this model is suitable for evaluating behavioural studies and in drug screening programs even for a long term study.
鱼藤酮是一种线粒体复合体I抑制剂，用作神经毒素剂以在大鼠中重现帕金森病（PD）的神经病理学和行为特征。由于通过不同给药途径急性和慢性暴露于不同剂量的鱼藤酮，已有死亡率的报道。低剂量在动物中产生PD症状需要更长时间。本研究旨在通过在白化大鼠纹状体的两个部位以单一中等剂量的鱼藤酮创建半帕金森氏症“部分”损伤模型，并通过行为参数和显微镜研究评估其毒性。
为了评估受损动物中由于多巴胺能神经元或其终末耗竭引起的所有运动缺陷，给受损动物施用抗帕金森病药物左旋多巴，其应抵消大鼠的运动缺陷。
通过立体定向将鱼藤酮以25μg/部位的剂量注入雄性Wistar白化大鼠纹状体的两个部位，诱导单侧部分损伤的PD模型。在注入鱼藤酮后的第7天、14天、21天和30天对大鼠进行神经行为活动测试，并与假手术组进行比较，并在第21天和30天处死以进行显微镜研究。损伤后第21天至30天给予左旋多巴，并与损伤组比较运动性能，并在第30天处死以进行组织学检查。行为学研究采用单因素方差分析，随后进行Tukey检验进行统计分析。
统计分析表明，与假手术组相比，在给予鱼藤酮后第14天和21天，运动不协调和姿势障碍等体征和症状非常显著（p<0.05）。在左旋多巴治疗的大鼠中，所有运动缺陷均得到逆转。神经元细胞死亡极少，并且检测到神经终末的发芽。在损伤组中，神经终末和纹状体神经元的变性呈进行性。
这些发现表明，以中等剂量纹状体内注入鱼藤酮可用于产生半帕金森氏症部分损伤动物模型而无任何死亡率。因此，该模型适用于评估行为学研究和药物筛选程序，甚至适用于长期研究。
