Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection.
Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection.
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DOI：
10.2147/ijn.s108329
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发表时间：
2016
影响因子：
8
通讯作者：
Nair M
中科院分区：
文献类型：
--
作者：
Atluri VS;Jayant RD;Pilakka-Kanthikeel S;Garcia G;Samikkannu T;Yndart A;Kaushik A;Nair M
虽然抗逆转录病毒治疗的引入降低了严重形式的神经认知障碍的患病率，但在全球50%的艾滋病毒感染患者中观察到人类免疫缺陷病毒（HIV）-1相关的神经认知障碍。已知血脑屏障对大多数抗逆转录病毒药物是不可渗透的。抗逆转录病毒药物成功进入大脑可能会诱导炎症反应，这可能会进一步诱导神经毒性。因此，替代抗逆转录病毒药物以减少HIV感染和神经毒性可能有助于减少在HIV感染患者中观察到的神经认知障碍。在这项研究中，我们探讨了磁性纳米颗粒（MNP）结合的金属蛋白酶组织抑制剂-1（TIMP 1）蛋白在降低HIV感染水平、氧化应激和恢复HIV感染的SK-N-MC神经母细胞瘤细胞中的棘密度方面的作用。我们没有观察到任何神经元的细胞毒性与自由的TIMP 1或在我们的研究中使用的MNP结合的TIMP 1。我们观察到显着减少HIV感染的溶液相和MNP结合的TIMP 1暴露的神经元细胞。此外，我们还观察到，与单独感染HIV的神经元细胞相比，两个试验组中活性氧的产生显著减少。为了观察可溶相TIMP 1和MNP结合的TIMP 1对HIV感染的神经元细胞中棘密度的影响，使用共聚焦显微镜。与单独感染HIV的细胞相比，我们观察到两个测试组的棘密度显著恢复，表明TIMP 1的神经保护作用。因此，我们的研究结果表明，MNP结合的TIMP 1递送方法跨越血脑屏障可用于减少HIV感染患者脑组织中的HIV感染性和神经元毒性。
Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients.