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Sulforaphane Attenuates Aβ Oligomers Mediated Decrease in Phagocytic Activity of Microglial Cells
Rajasekhar Reddy Chilakala1, Aparna Lakshmi Manchikalapudi1, Ashok Kumar1
1Department of Biotechnology, National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar 382355, Gujarat, India.
Abstract:
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.
Insights
Sulforaphane (SFN) may enhance microglial phagocytic activity impaired by amyloid beta oligomers (Aβo). This study investigated how Aβo affect microglia, finding SFN treatment improved their ability to clear Aβo without increasing inflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, are crucial in neurodegenerative diseases like Alzheimer's.
- Their role in clearing protein aggregates, such as amyloid beta (Aβ), is increasingly recognized but affected by aging and disease.
- Microglial function can be either beneficial or detrimental, depending on the stimulus, highlighting the need to harness beneficial properties.
Purpose of the Study:
- To investigate the impact of toxic amyloid beta oligomers (Aβo) on microglial phagocytic activity.
- To determine if Sulforaphane (SFN) can restore or enhance microglial phagocytosis of Aβo.
- To assess the effect of Aβo and SFN on microglial pro-inflammatory responses.
Main Methods:
- Exposure of microglia to varying concentrations of amyloid beta oligomers (Aβo).
- Assessment of microglial phagocytic activity and cell survival.
- Gene expression analysis for genes regulating phagocytosis.
- Treatment with Sulforaphane (SFN) and evaluation of its effects on phagocytosis and pro-inflammatory mediators.
Main Results:
- Low concentrations of Aβo decreased microglial phagocytic activity without causing significant toxicity.
- High concentrations of Aβo were toxic and modulated genes involved in phagocytosis.
- SFN treatment enhanced the phagocytic activity of Aβo-treated microglia.
- Low-dose Aβo and SFN treatments did not increase pro-inflammatory mediator levels.
Conclusions:
- Microglial phagocytic activity is impaired by amyloid beta oligomers (Aβo) in a dose-dependent manner.
- Sulforaphane (SFN) shows potential in ameliorating Aβo-induced reduction in microglial phagocytosis.
- Targeting microglial phagocytosis with agents like SFN could be a therapeutic strategy for Alzheimer's disease, potentially without exacerbating inflammation.
