Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Department of Biochemistry, Babu Banarasi Das (BBD) College of Dental Sciences, BBD University, Lucknow, 227 015, Uttar Pradesh, India.
Mol Neurobiol. 2018 Mar;55(3):2333-2339. doi: 10.1007/s12035-017-0491-9. Epub 2017 Mar 25.
Microgliosis and inflammation are major wrongdoers in cypermethrin-induced Parkinsonism along with oxidative stress, mitochondrial dysfunction and α-synuclein aggregation. Dopamine depletion could alter dendritic morphology, length and spine number in the striatum. Present study investigated the effect of ibuprofen on the dendritic morphology, length and spine density in cypermethrin PD model. Male pups were treated intraperitoneally with cypermethrin during postnatal days followed by adulthood to induce Parkinsonism using standard procedure along with controls. Subsets of animals were pre-treated with ibuprofen 2 h prior to cypermethrin treatment during adulthood. Standard methods were used to confirm Parkinsonism/neuroprotection. Striatal dendritic morphology, length, spine number and expression of synaptophysin and postsynaptic density protein-95 (PSD-95) along with the nigrostriatal pro-inflammatory and apoptotic proteins were measured. Cypermethrin induced Parkinsonian traits and attenuated the dendritic length, spine number and expression of synaptophysin and PSD-95. While cypermethrin increased the expression of interleukin-1β, interleukin-4, interferon-γ, inducible nitric oxide synthase, caspase-3, caspase-9 and B-cell lymphoma (Bcl)-xl proteins, it attenuated Bcl-2 expression. Ibuprofen normalized the changes in dendritic morphology, length, spine number and expression of synaptophysin, PSD-95, and pro-inflammatory and apoptotic proteins. Results demonstrate that cypermethrin induces inflammation and alters dendritic morphology, length and spine number, which are encountered by ibuprofen.
小胶质细胞增生和炎症是除氧化应激、线粒体功能障碍和α-突触核蛋白聚集外，氯菊酯诱导的帕金森病的主要罪魁祸首。多巴胺耗竭可改变纹状体树突的形态、长度和棘突数量。本研究探讨了布洛芬对氯菊酯 PD 模型树突形态、长度和棘突密度的影响。雄性幼鼠在出生后第天经腹腔内给予氯菊酯处理，然后在成年期用标准程序诱导帕金森病，同时设立对照组。亚组动物在成年期给予氯菊酯处理前 2 小时预先给予布洛芬处理。采用标准方法确认帕金森病/神经保护。测量纹状体树突形态、长度、棘突数量以及突触小体蛋白和突触后密度蛋白-95（PSD-95）的表达，同时测量黑质纹状体促炎和凋亡蛋白。氯菊酯诱导帕金森病特征，并减弱树突长度、棘突数量和突触小体蛋白及 PSD-95 的表达。氯菊酯增加白细胞介素-1β、白细胞介素-4、干扰素-γ、诱导型一氧化氮合酶、半胱天冬酶-3、半胱天冬酶-9 和 B 细胞淋巴瘤（Bcl）-xl 蛋白的表达，同时减弱 Bcl-2 表达。布洛芬使树突形态、长度、棘突数量和突触小体蛋白、PSD-95 以及促炎和凋亡蛋白的变化正常化。结果表明，氯菊酯诱导炎症并改变树突形态、长度和棘突数量，这些变化可被布洛芬所纠正。
