Yadav Satyndra Kumar, Pandey Shivani, Singh Babita
Department of Biological Science, Yathartha Institute, Lucknow 226014, India.
Department of Biochemistry, KGMU, Lucknow 226003, India.
J Chem Neuroanat. 2017 Nov;85:50-59. doi: 10.1016/j.jchemneu.2017.07.002. Epub 2017 Jul 12.
Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly reduced the MPTP induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse with cognitive deficit as compared to levodopa treatment.
帕金森病（PD）是老年人群中最常见的神经退行性疾病之一。目前，许多研究正在进行，以寻找适合且有效的PD治疗方法，重点是使用草药植物。在本研究中，在具有认知缺陷的PD的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）模型中评估了雌激素的神经保护作用，并与左旋多巴（LD）进行了比较，左旋多巴是一种用于治疗PD的报道充分的神经保护剂。将24只瑞士白化小鼠随机分为四组：对照组、MPTP组、MPTP + LD组和MPTP + 雌激素组。使用转棒试验、脚印试验、窄梁行走试验和悬挂试验研究了LD和雌激素处理小鼠的行为恢复情况。使用Y迷宫和莫里斯水迷宫研究了LD和雌激素处理小鼠的非运动行为恢复情况。此外，我们在小鼠脑的前额叶皮质以及黑质纹状体区域进行了生化测试，即过氧化氢酶、脂质和亚硝酸盐测试。我们还在小鼠脑的前额叶皮质和黑质纹状体区域进行了乙酰胆碱酯酶活性测试。通过酪氨酸羟化酶（TH）免疫染色估计黑质（SN）区域多巴胺神经元的恢复情况。雌激素治疗比左旋多巴更有效地恢复了MPTP诱导的所有缺陷。雌激素治疗恢复了SN区域中TH阳性细胞的数量。雌激素治疗显著提高了SN区域以及前额叶皮质区域中过氧化氢酶的水平，降低了脂质和亚硝酸盐的水平。值得注意的是，雌激素的作用大于左旋多巴所引起的作用。MPTP组中乙酰胆碱酯酶活性显著增加，并且发现雌激素和左旋多巴治疗均可使其降低，尽管雌激素治疗组中活性的降低非常显著。我们的结果表明，与左旋多巴治疗相比，雌激素治疗显著降低了MPTP诱导的神经毒性，这在具有认知缺陷的帕金森病小鼠中表现为氧化损伤、生理异常和免疫组化变化的减少。
