Sil Susmita, Ghosh Tusharkanti, Ghosh Rupsa, Gupta Pritha
Neurophysiology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009, West Bengal, India.
Neurophysiology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009, West Bengal, India.
J Neuroimmunol. 2017 Feb 15;303:51-61. doi: 10.1016/j.jneuroim.2016.12.007. Epub 2016 Dec 13.
Intracerebroventricular (i.c.v.) injection of colchicine induces neurodegeneration, memory impairments and changes of some systemic immune responses in rats. Though the role of cox 2 in these colchicine induced changes have been evaluated, the influence of nitric oxide synthase (NOS) remains to be studied. The present study was designed to assess the role of NOS on the i.c.v. colchicine induced neurodegeneration, memory impairments and changes of some systemic immune responses by inhibiting its activity with aminoguanidine. In the present study the impairments of working and reference memories, neurodegeneration (chromatolysis and plaque formation) and changes of neuroinflammatory markers in the hippocampus (increased TNF α, IL 1β, ROS and nitrite) along with changes of serum inflammatory markers (TNF α, IL 1β, ROS and nitrite) and alteration of systemic immune responses (higher phagocytic activity of blood WBC and splenic PMN, higher cytotoxicity and lower leukocyte adhesion inhibition index of splenic MNC) were measured in the intracerebroventricular colchicine injected rats (ICIR). Administration of aminoguanidine (p.o. 30/50mg/kg body weight) to ICIR resulted in recovery of neuroinflammation and partial prevention of neurodegeneration which could be corroborated with the partial recovery of memory impairments in this model. The recovery of serum inflammatory markers and the systemic immune responses in ICIR was also observed after administration of aminoguanidine. Therefore, the present study shows that aminoguanidine can protect the colchicine induced neurodegeneration, memory impairments, and changes of systemic immune systemic responses in ICIR by inhibiting the iNOS.
脑室内注射秋水仙碱可诱导大鼠神经退行性变、记忆障碍以及一些全身免疫反应的改变。尽管已经评估了环氧化酶2在这些秋水仙碱诱导的变化中的作用，但一氧化氮合酶（NOS）的影响仍有待研究。本研究旨在通过用氨基胍抑制其活性来评估NOS在脑室内注射秋水仙碱诱导的神经退行性变、记忆障碍以及一些全身免疫反应变化中的作用。在本研究中，测量了脑室内注射秋水仙碱的大鼠（ICIR）的工作记忆和参考记忆损伤、神经退行性变（染色质溶解和斑块形成）以及海马中神经炎症标志物的变化（肿瘤坏死因子α、白细胞介素1β、活性氧和亚硝酸盐增加），同时还测量了血清炎症标志物的变化（肿瘤坏死因子α、白细胞介素1β、活性氧和亚硝酸盐）以及全身免疫反应的改变（血液白细胞和脾多形核白细胞的吞噬活性更高、脾单核细胞的细胞毒性更高以及白细胞黏附抑制指数更低）。给ICIR大鼠口服氨基胍（30/50mg/kg体重）可导致神经炎症的恢复和神经退行性变的部分预防，这与该模型中记忆损伤的部分恢复相一致。给予氨基胍后，还观察到ICIR大鼠血清炎症标志物和全身免疫反应的恢复。因此，本研究表明，氨基胍可以通过抑制诱导型一氧化氮合酶来保护ICIR大鼠免受秋水仙碱诱导的神经退行性变、记忆障碍以及全身免疫反应的变化。
