Sub-chronic Mptp-Induced Parkinsonism: Selective Sensitivity of the Balb/C Mice and the Prophylactic Roles of Nigella Sativa Oil

Parkinsonism is a degenerative neurological syndrome characterised by dopamine deficiency in the basal ganglia. Despite ages of research, there is still lack of holistic and side-effect-free therapy for the disease. Nigella sativa is a multi-potent plant known for its historical and scientifically proven therapeutic potentials in the brain and other body organs. Despite the validity debates on the use of BALB/c mice strains in the modelling of Parkinsonism using MPTP, this study re-appraised the sensitivity versus resistance of the BALB/c mice strain to MPTP and further investigated the possible neuro-thrapeutic role of Nigella sativa oil (NSO) in the Parkinsonic endophenotypes elicited by MPTP in the BALB/c strain. Body weights, relative brain weights, striatal dopamine, striatal neuron density and recognition memory were studied in thirty-two (32) male albino mice, weighing between 18g -25g. They were divided equally into Control (administered with normal feed for 5 days), MPTP (administered with 18mg/kg MPTP i.p for 5 days), NS (administered with 1ml/kgbw NSO p.o. for 5 days), and NS+MPTP (administered with 1ml/kgbw NSO p.o. followed by 18mg/kg MPTP i.p for 5 days). Recognition memory was assayed through Novel Object Recognition test (NORT), and the animals were weighed and euthanised 24 hours after last administration. The brains were excised and the striatum assayed neurochemically for dopamine and illustrated histologically for neuronal density using the H&E stain. Parkinsonic traits such as mild tremor, significant down-regulation of dopamine and striatal neurons (p<0.05) were recorded in the BALB/c mice administered with MPTP only, confirming MPTP-sensitivity for these features. However, significant increase (p<0.05) in appetite, body weight, brain-body weight ratio, and recognition memory was also recorded in the MPTP-administered mice, though Nigella sativa was significantly prophylactic against the negative Parkinsonic features, and ‘moderative’ of the up-regulations induced by MPTP. While this suggests selective MPTP sensitivity and resistance in BALB/c strains, this study recommends the investigation of possible beneficial potentials of MPTP as observed. The research was conducted in conformance with the Animal Research Ethics Committee (AREC) guidelines of the Olabisi Onabanjo University.

帕金森综合征（Parkinsonism）是一种以基底神经节（basal ganglia）多巴胺缺乏为特征的退行性神经系统综合征。尽管历经数十年研究，目前仍缺乏针对该疾病的全面且无不良反应的治疗方案。黑种草（Nigella sativa）是一种多效性植物，其在大脑及其他身体器官中的治疗潜力已得到历史记载与科学证实。尽管关于使用BALB/c小鼠品系构建MPTP诱导的帕金森综合征模型存在有效性争议，本研究重新评估了BALB/c小鼠品系对MPTP的敏感性与抗性，并进一步探究了黑种草油（Nigella sativa oil, NSO）对该品系小鼠中MPTP诱发的帕金森样表型的潜在神经治疗作用。
本研究选取32只体重介于18g~25g的雄性白化小鼠，对其体重、相对脑重、纹状体多巴胺水平、纹状体神经元密度与识别记忆进行检测。将小鼠平均分为四组：对照组（给予正常饲料饲养5天）、MPTP组（腹腔注射18mg/kg MPTP，持续5天）、NS组（经口给予1ml/kg体重的NSO，持续5天）以及NS+MPTP组（先经口给予1ml/kg体重的NSO，随后腹腔注射18mg/kg MPTP，持续5天）。
识别记忆采用新物体识别实验（Novel Object Recognition test, NORT）进行检测。末次给药24小时后，对小鼠称重并实施安乐死，摘取脑组织，对纹状体进行多巴胺水平的神经化学检测，并通过苏木精-伊红（H&E）染色开展神经元密度的组织学观察。
仅接受MPTP给药的BALB/c小鼠出现了轻度震颤、多巴胺与纹状体神经元显著下调（p<0.05）等帕金森样特征，证实了该品系小鼠对这些表型的MPTP敏感性。同时，仅接受MPTP给药的小鼠食欲、体重、脑体比与识别记忆均出现显著升高（p<0.05）；而黑种草可显著预防帕金森样负面特征的出现，并对MPTP诱导的升高效应起到“调节”作用。
尽管这一结果提示BALB/c品系小鼠存在选择性的MPTP敏感性与抗性，本研究建议针对本次观测到的MPTP潜在有益潜力开展进一步研究。本研究严格遵循奥拉比西·奥纳班乔大学动物研究伦理委员会（Animal Research Ethics Committee, AREC）的指导原则开展。