Czub M, Czub S, Gosztonyi G, Koutsilieri E, Sopper S, Müller J G, Gerlach M, Riederer P, ter Meulen V
Institut für Virologie, Universität Wurzburg, Germany.
J Neurovirol. 1999 Oct;5(5):458-64. doi: 10.3109/13550289909045374.
Upon inoculation into neonatal rats, murine leukemia virus (MuLV) NT40 causes a non-inflammatory degeneration of the central nervous system. While microglia cells appear to be the major target cells within the brain parenchyma for neurovirulent MuLV, degenerating neurons do not express retroviral gene products. In order to protect rats from neuronal damage we treated retrovirally infected rats once with monoamine oxidase (MAO) B inhibitor Selegiline which--under different conditions--exerts neuroprotective effects. Unexpectedly, when administered at 17 days post-infection (d.p.i.) a single intraperitoneal dose of Selegilin (1 mg/kg bodyweight) significantly shortened the incubation period for neurological disease. In contrast, Selegiline given in a lower dosage (0.05 mg/kg bodyweight) and/or at a different time point (13 d.p.i.) at the low (0.05 mg/kg bodyweight) and the high dose (1.0 mg/kg bodyweight) had no effect on the outcome of neurological disease. Animals treated with Selegiline (1.0 mg/kg bodyweight at 17 d.p.i.) contained higher amounts of viral loads in the CNS, higher numbers of brain cells expressing major histocompatibility complex class II molecules, and exhibited inhibition of MAO-B in comparison to untreated yet infected (control) animals. Supposedly, Selegiline activated the major target cell population of the CNS for MuLV-NT40, microglia, with the consequence of enhanced susceptibility for retroviral infection and triggered endogenous mechanism(s) involved in the pathogenesis of retroviral neurodegeneration.
将鼠白血病病毒（MuLV）NT40接种到新生大鼠体内后，会引起中枢神经系统的非炎症性退化。虽然小胶质细胞似乎是脑实质内对神经毒性MuLV的主要靶细胞，但退化的神经元不表达逆转录病毒基因产物。为了保护大鼠免受神经元损伤，我们用单胺氧化酶（MAO）B抑制剂司来吉兰对逆转录病毒感染的大鼠进行了一次治疗，该抑制剂在不同条件下具有神经保护作用。出乎意料的是，在感染后17天（d.p.i.）腹腔注射单剂量司来吉兰（1毫克/千克体重）会显著缩短神经疾病的潜伏期。相比之下，以较低剂量（0.05毫克/千克体重）和/或在不同时间点（13 d.p.i.）给予低剂量（0.05毫克/千克体重）和高剂量（1.0毫克/千克体重）的司来吉兰对神经疾病的结果没有影响。与未治疗但已感染的（对照）动物相比，用司来吉兰治疗的动物（在17 d.p.i.时给予1.0毫克/千克体重）中枢神经系统中的病毒载量更高，表达主要组织相容性复合体II类分子的脑细胞数量更多，并且表现出MAO-B的抑制。据推测，司来吉兰激活了MuLV-NT40在中枢神经系统中的主要靶细胞群体——小胶质细胞，导致对逆转录病毒感染的易感性增强，并触发了逆转录病毒神经变性发病机制中涉及的内源性机制。
