BACKGROUND AND AIM Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. MATERIALS AND METHODS Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 ml); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. RESULTS There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). CONCLUSION Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

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使用拉米夫定模拟大鼠小脑肢体失认和空间记忆受损：一项初步研究

背景和目的 神经变性与联合抗逆转录病毒疗法 (cART) 的使用有关。本研究旨在确定 cART 的任何成分是否会引起小脑肢体辨距障碍和空间记忆障碍。材料与方法 40 只成年雄性 Wistar 大鼠随机分为 4 组（n = 10）：对照组（蒸馏水 0.5 ml）；对照组（蒸馏水 0.5 ml）；替诺福韦（6毫克/公斤）；拉米夫定（6 毫克/公斤）和依非韦伦（12 毫克/公斤）。进行了以下神经行为研究：旷场、光束行走和莫里斯水迷宫。CD 68 和 GFAP 的免疫组织化学用于检测神经炎症和神经变性。结果治疗组海马固缩锥体细胞和小脑鬼浦肯野细胞明显增多。拉米夫定和依非韦伦组的氧化应激也显着增加。此外，与对照相比，拉米夫定导致小胶质细胞和星形细胞活性显着增加（分别为 p < 0.001、0.05）。旷场测试显示，与对照 (50.6) 相比，依非韦伦、拉米夫定和替诺福韦 (平均值分别为：26.4、4.6、17.4) 的品系穿越性能显着下降 (p < 0.0001)。拉米夫定组的梳理行为（p < 0.05）和饲养行为（p < 0.01）也显着减少。然而，与对照组相比，依非韦伦 (p < 0.01) 和拉米夫定 (p < 0.0001) 的步行潜伏期增加。与对照组相比，依非韦伦（p < 0.05）和拉米夫定（p < 0.0001）的后肢滑倒显着增加。同样，与对照组相比，拉米夫定和替诺福韦暴露组识别隐藏平台的时间显着延迟（p < 0.05）。结论 拉米夫定改变了小脑脊髓束的传出刺激，从而导致运动障碍。退化的浦肯野纤维可能引起海马体明显的神经变性，导致空间记忆受损。