Sil Susmita, Goswami Ananda Raj, Dutta Goutam, Ghosh Tusharkanti
Neurophysiology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, India.
Neuroimmunomodulation. 2014;21(6):304-21. doi: 10.1159/000357735. Epub 2014 Mar 21.
The components of the immune system have been indicated to be linked with the neurotoxicity in Alzheimer's disease (AD). The participation of the immune system in the neurodegeneration in a rat model of colchicine-induced AD has not been explored.
In the present study, hippocampal neurodegeneration along with reactive oxygen species (ROS), nitrite and TNF-α in the hippocampus and some systemic immune responses were measured after 15 and 21 days of intracerebroventricular colchicine injection in rats and again after oral administration of different doses of the anti-inflammatory drug naproxen in AD rats.
Chromatolysis and amyloid plaques were found along with higher ROS, nitrite and TNF-α levels in the hippocampus of colchicine-induced AD rats, and these changes were prevented by naproxen in a dose-dependent manner. Alterations in immunological parameters [increased phagocytic activity of white blood cells and splenic polymorphonuclear cells (PMN), increased cytotoxicity and decreased leucocyte adhesive inhibition index (LAI) of splenic mononuclear cells (MNC)] were also observed in colchicine-injected rats, which showed a dose-dependent recovery after oral administration of naproxen in AD rats. The number of plaques, chromatolysis of Nissl granules, TNF-α, nitrite and ROS levels in the hippocampus, phagocytic activity of splenic PMN and LAI of splenic MNC in AD rats showed greater changes in the 21- than in the 15-day study, and the recovery of these parameters after administration of naproxen differed between the two study durations.
The present study shows that colchicine-induced neurodegeneration is time dependent and mediated by cyclooxygenase-induced neuroinflammation, which is reflected in the systemic immunological responses.
免疫系统的组成部分已被表明与阿尔茨海默病（AD）中的神经毒性有关。免疫系统在秋水仙碱诱导的AD大鼠模型的神经退行性变中的参与情况尚未得到研究。
在本研究中，在大鼠脑室内注射秋水仙碱15天和21天后，以及在AD大鼠口服不同剂量的抗炎药物萘普生后，再次测量海马神经退行性变以及海马中的活性氧（ROS）、亚硝酸盐和肿瘤坏死因子-α（TNF-α），并检测一些全身免疫反应。
在秋水仙碱诱导的AD大鼠海马中发现了染色质溶解和淀粉样斑块，同时海马中的ROS、亚硝酸盐和TNF-α水平升高，而萘普生以剂量依赖的方式阻止了这些变化。在注射秋水仙碱的大鼠中还观察到免疫参数的改变[白细胞和脾多形核细胞（PMN）的吞噬活性增加、脾单核细胞（MNC）的细胞毒性增加和白细胞粘附抑制指数（LAI）降低]，在AD大鼠口服萘普生后这些改变呈剂量依赖性恢复。AD大鼠海马中的斑块数量、尼氏小体染色质溶解、TNF-α、亚硝酸盐和ROS水平、脾PMN的吞噬活性以及脾MNC的LAI在21天研究中比15天研究中的变化更大，并且在两个研究时间段内给予萘普生后这些参数的恢复情况有所不同。
本研究表明，秋水仙碱诱导的神经退行性变具有时间依赖性，并且由环氧化酶诱导的神经炎症介导，这在全身免疫反应中得到体现。
