Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 04, 2025 2 days, 3 hours, 13 minutes ago
Medical News: The global pandemic caused by SARS-CoV-2 continues to reveal new dimensions of its impact on human health. Beyond respiratory complications, mounting evidence highlights its significant effects on the nervous system. Researchers from Tulane University School of Medicine and Tulane Brain Institute in New Orleans, Louisiana, have made a startling discovery about how folate deficiency might exacerbate these neurological impacts. This study shines a light on the mechanisms through which folate metabolism influences brain health, particularly in the context of COVID-19 infections.
Folate Deficiency Aggravates COVID-19 Impacts on Brain Health
Folate, a crucial B-vitamin, plays an essential role in brain function and maintaining vascular health. However, a common genetic variation in the methylene tetrahydrofolate reductase (MTHFR) enzyme significantly alters folate metabolism, increasing vulnerability to various neurological disorders. This
Medical News report delves into the study's findings, highlighting how SARS-CoV-2 exacerbates vascular and neurological damage under conditions of folate deficiency.
Study Focus and Methodology
The research team aimed to explore the link between folate metabolism, mediated by the MTHFR enzyme, and the neuroinflammatory and vascular damage caused by SARS-CoV-2. Specifically, they studied mice genetically modified to have reduced MTHFR activity (Mthfr heterozygous knockout mice) and compared their responses to SARS-CoV-2 infection with normal mice. These mice were inoculated with a mouse-adapted strain of SARS-CoV-2 capable of mimicking human infection patterns.
Alongside in vivo experiments, the team used in vitro methods to examine the effects of folate deficiency in mouse brain microvascular endothelial cells (bEnd.3). These cells were cultured in both folate-sufficient and folate-deficient environments and exposed to SARS-CoV-2 spike proteins. The experiments measured changes in cellular and molecular markers of blood-brain barrier integrity and inflammation.
Key Findings and Insights
The study uncovered compelling evidence that folate deficiency worsens SARS-CoV-2-induced damage to the brain’s vascular system. One significant observation was the exacerbation of blood-brain barrier disruption in mice with Mthfr deficiency when infected with SARS-CoV-2. The barrier, vital for protecting the brain from harmful substances, showed marked vulnerability in the absence of adequate folate.
-Weight Loss and Viral Load
Mice with reduced MTHFR activity displayed more pronounced disease-associated weight loss - 10.5% compared to 8.5% in normal mice. Viral load measurements in the lungs revealed a higher burden in the Mthfr knockout group, with 6.3 × 10⁷ viral copies per 100 ng RNA versus 5.8 × 10⁷ copies in wild-type mice.
-Blood-Brain Barrier Integrity
A critical part of the study was assessing the integrity of the blood-brain barrier. Molecular markers such as ZO-
1, a tight junction protein essential for the barrier’s function, were significantly reduced in infected Mthfr knockout mice compared to their normal counterparts. Immunostaining showed a clear reduction in ZO-1 expression in the cortical regions of the brain, suggesting a compromised barrier that could allow harmful substances to infiltrate the brain more readily.
-Cellular and Molecular Markers
The in vitro experiments provided further clarity. In brain endothelial cells cultured under folate-deficient conditions, the expression of critical tight junction proteins such as Claudin-5 and Occludin was significantly decreased. When these cells were exposed to SARS-CoV-2 spike proteins, Claudin-5 levels dropped even further, underscoring the synergistic damage caused by folate deficiency and viral infection.
-Inflammatory Responses
Another notable finding was the reduced activation of microglial cells in Mthfr-deficient mice. While this might seem beneficial, microglial activation is part of the brain’s natural immune response to infection. A lack of adequate response could signify a compromised ability to repair and defend against damage.
Implications for Public Health
The findings from this study raise important questions about the role of nutrition in managing and mitigating the effects of COVID-19. Folate deficiency, already a global health concern, may pose an additional risk factor for individuals infected with SARS-CoV-2. The study suggests that populations with a high prevalence of MTHFR genetic variations might face an increased burden of post-COVID neurological complications, including vascular dementia and cognitive decline.
Conclusions and Future Directions
The study conducted by researchers from Tulane University emphasizes the critical intersection between nutrition, genetics, and infectious diseases. It highlights how a simple micronutrient deficiency can amplify the devastating impacts of a viral infection on the nervous system. The findings underscore the importance of maintaining adequate folate levels to protect against COVID-19-related complications.
Moreover, the research opens avenues for therapeutic interventions. Addressing folate deficiency through dietary supplements or fortified foods might serve as a cost-effective strategy to mitigate the neurological impacts of SARS-CoV-2. However, further research is needed to validate these findings in human populations and explore the efficacy of such interventions.
The study findings were published in the peer-reviewed journal: Alzheimer’s & Dementia.
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.092234
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