Previous studies showed that persons living with HIV (PLWH) demonstrate higher brain prefrontal cortex neuroinflammation and immunoproteasome expression compared to HIV-negative individuals; these associate positively with HIV levels. Lower expression of the antioxidant enzyme heme oxygenase 1 (HO-1) was observed in PLWH with HIV-associated neurocognitive impairment (HIV-NCI) compared to neurocognitively normal PLWH. We hypothesized that similar expression patterns occur throughout cortical, subcortical, and brainstem regions in PLWH, and that neuroinflammation and immunoproteasome expression associate with lower expression of neuronal markers. We analyzed autopsied brains (15 regions) from 9 PLWH without HIV-NCI and 7 matched HIV-negative individuals. Using Western blot and RT-qPCR, we quantified synaptic, inflammatory, immunoproteasome, endothelial, and antioxidant biomarkers, including HO-1 and its isoform heme oxygenase 2 (HO-2). In these PLWH without HIV-NCI, we observed higher expression of neuroinflammatory, endothelial, and immunoproteasome markers in multiple cortical and subcortical regions compared to HIV-negative individuals, suggesting a global brain inflammatory response to HIV. Several regions, including posterior cingulate cortex, globus pallidus, and cerebellum, showed a distinct pattern of higher type I interferon (IFN)-stimulated gene and immunoproteasome expression. PLWH without HIV-NCI also had (i) stable or higher HO-1 expression and positive associations between (ii) HO-1 and HIV levels (CSF, plasma) and (iii) HO-1 expression and neuroinflammation, in multiple cortical, subcortical, and brainstem regions. We observed no differences in synaptic marker expression, suggesting little, if any, associated neuronal injury. We speculate that this may reflect a neuroprotective effect of a concurrent HO-1 antioxidant response despite global neuroinflammation, which will require further investigation.

先前的研究表明，与 HIV 阴性个体相比，HIV 感染者 (PLWH) 表现出更高的大脑前额叶皮层神经炎症和免疫蛋白酶体表达；这些与 HIV 水平呈正相关。与神经认知正常的 PLWH 相比，在患有 HIV 相关神经认知障碍 (HIV-NCI) 的 PLWH 中观察到抗氧化酶血红素加氧酶 1 (HO-1) 的表达较低。我们假设类似的表达模式发生在 PLWH 的整个皮质、皮质下和脑干区域，并且神经炎症和免疫蛋白酶体表达与神经元标记物的低表达相关。我们分析了来自 9 名没有 HIV-NCI 的 PLWH 和 7 名匹配的 HIV 阴性个体的尸检大脑（15 个区域）。使用蛋白质印迹和 RT-qPCR，我们量化了突触、炎症、免疫蛋白酶体、内皮和抗氧化生物标志物，包括 HO-1 及其同种型血红素加氧酶 2 (HO-2)。在这些没有 HIV-NCI 的 PLWH 中，我们观察到与 HIV 阴性个体相比，多个皮质和皮质下区域的神经炎症、内皮和免疫蛋白酶体标志物的表达更高，这表明对 HIV 的整体脑炎症反应。几个区域，包括后扣带回皮层、苍白球和小脑，显示出较高的 I 型干扰素 (IFN) 刺激基因和免疫蛋白酶体表达的独特模式。没有 HIV-NCI 的 PLWH 还具有 (i) 稳定或更高的 HO-1 表达以及 (ii) HO-1 与 HIV 水平（CSF、血浆）和 (iii) HO-1 表达与神经炎症之间的正相关性，在多个皮质中，皮层下和脑干区域。我们观察到突触标记表达没有差异，表明几乎没有相关的神经元损伤。我们推测这可能反映了同时发生的 HO-1 抗氧化反应的神经保护作用，尽管存在全身神经炎症，这将需要进一步研究。