Abstract
Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Once neuronal cells are infected, the virus is capable of modulating cell metabolism, leading to neurotoxicity and cellular death. The negative effect of ZIKV in neuron cells has been characterized. However, the description of molecules capable of reversing these cytotoxic effects is still under investigation. In this context, it has been largely demonstrated that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is highly neuroprotective. Here, we hypothesized that DHA’s neuroprotective proprieties could have an influence on ZIKV-induced neurotoxicity in SH-SY5Y cells. Our data showed that pre-treatment of SH-SY5Y cells with DHA increased the cell viability and proliferation in ZIKV-infected cells. Moreover, DHA triggered an anti-inflammatory response in those infected cells. Besides, DHA was capable of restoring mitochondria function and number in ZIKV-infected SH-SY5Y cells. In addition, cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at different times of infection. Taking together, these results demonstrated that DHA has a potential anti-inflammatory and neuroprotective effect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus.
Highlights
Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes
We observed that ZIKV significantly reduced SH-SY5Y cells viability from 72 hours forward compared to uninfected cells
At 96 hours, ZIKV triggered a 50% loss of SH-SY5Y cells viability. Considering these results, we decided to investigate whether omega-3 docosahexaenoic acid (DHA) could protect SH-SY5Y cells cells from cell viability loss observed at 96 hours of infection
Summary
Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at different times of infection Taking together, these results demonstrated that DHA has a potential anti-inflammatory and neuroprotective effect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus. Specific ZIKV proteins are capable of inhibiting Akt-mTOR pathway in neuronal stem cells, which plays essential role on neurogenesis process, cell maturation and migration[9,10] Such mechanisms act synergistically to induce neuronal apoptotic cell death and loss of massive cell population during brain development and it can be accompanied by activation of inflammatory response[7,11,12]. The central impact of DHA in the organism can be related to neuroprotection, increasing longevity of neuronal cells and decreasing neurodegeneration, inflammation and cognitive decline[22]
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