Chilakala Rajasekhar Reddy, Manchikalapudi Aparna Lakshmi, Kumar Ashok, Sunkaria Aditya
Department of Biotechnology, National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar 382355, Gujarat, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar 382355, Gujarat, India; Department of Biotechnology, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
Neuroscience. 2020 Mar 1;429:225-234. doi: 10.1016/j.neuroscience.2020.01.002. Epub 2020 Jan 23.
Microglia are the brain mononuclear phagocytes which plays a key role in neurodegenerative diseases, like Alzheimer's. Till date, microglia have been explored mostly for their neuro-inflammatory functions. Recent studies have shifted their focus towards less explored functions which involve non-autonomous clearance of protein aggregates. However, these functions are significantly affected by aging and neurodegeneration. In Alzheimer's disease (AD), microglia have been reported to clear amyloid beta (Aβ) deposits via phagocytosis or release various pro-inflammatory cytokines. Whether microglia could be beneficial or detrimental to the brain, it all depends upon the type and strength of stimulus. So, if their beneficial properties could be selectively harnessed without activating pro-inflammatory response, a potential therapeutic strategy could be developed to check the formation of protein aggregates like Aβ. In the present study, we have checked the effect of toxic amyloid beta oligomers (Aβo) on the microglial phagocytic activity. Our findings revealed that at lower concentrations, Aβo are not toxic to the cells and they can survive even with longer exposures but with decreased phagocytic activity. However, at higher concentrations Aβo become toxic and resulted in modulation of various genes which regulates microglial phagocytic activity. Sulforaphane (SFN) treatment has shown to induce the phagocytic activity of Aβo treated microglial cells. In addition, low dose Aβo and SFN treatment have not shown modulation in the levels of pro-inflammatory mediators of microglia. Taken together, these findings suggest that SFN treatment may ameliorate the Aβo mediated decrease in microglial phagocytic activity.
小胶质细胞是脑内单核吞噬细胞，在神经退行性疾病（如阿尔茨海默病）中起关键作用。迄今为止，对小胶质细胞的研究主要集中在其神经炎症功能方面。最近的研究已将重点转向较少探索的功能，这些功能涉及蛋白质聚集体的非自主清除。然而，这些功能会受到衰老和神经退行性变的显著影响。在阿尔茨海默病（AD）中，据报道小胶质细胞可通过吞噬作用清除淀粉样β蛋白（Aβ）沉积物或释放各种促炎细胞因子。小胶质细胞对大脑是有益还是有害，这完全取决于刺激的类型和强度。因此，如果能够在不激活促炎反应的情况下选择性地利用其有益特性，就有可能开发出一种潜在的治疗策略来抑制Aβ等蛋白质聚集体的形成。在本研究中，我们检测了有毒淀粉样β寡聚体（Aβo）对小胶质细胞吞噬活性的影响。我们的研究结果表明，在较低浓度下，Aβo对细胞无毒，即使长时间暴露它们也能存活，但吞噬活性会降低。然而，在较高浓度下，Aβo变得有毒，并导致调节小胶质细胞吞噬活性的各种基因发生变化。萝卜硫素（SFN）处理已显示可诱导Aβo处理的小胶质细胞的吞噬活性。此外，低剂量Aβo和SFN处理并未显示小胶质细胞促炎介质水平的变化。综上所述，这些研究结果表明，SFN处理可能改善Aβo介导的小胶质细胞吞噬活性下降。
