COVID-19 Causes the Upregulation of Neuroinflammation-Associated Genes in the Brain

COVID-19 News: Understanding COVID-19's Impact on the Brain
COVID-19, the disease caused by the SARS-CoV-2 virus, has had an unparalleled impact on global health, primarily recognized for its severe respiratory symptoms. However, emerging research highlights another critical aspect of this virus: its significant effects on the brain. Recent studies by researchers from the College of Medicine, Korea University Guro Hospital-Republic of Korea and Georgia State University, Atlanta-USA that is covered in this COVID-19 News report, reveal that COVID-19 can trigger substantial changes in the brain, particularly by upregulating genes associated with neuroinflammation, leading to various neurological complications.


COVID-19 Causes the Upregulation of Neuroinflammation-Associated
Genes in the Brain

What is Neuroinflammation?
Neuroinflammation refers to inflammation within the central nervous system (CNS), encompassing the brain and spinal cord. This condition is a hallmark of many neurological diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Symptoms of neuroinflammation can range from headaches and cognitive dysfunction to seizures and long-term neurological deficits. Understanding the genetic changes that SARS-CoV-2 induces in the brain is crucial for grasping how COVID-19 impacts neurological health.
 
The Mouse Model Study: A Deep Dive
To investigate COVID-19's effects on the brain, researchers utilized a special type of laboratory mice known as K18-hACE2 mice. These mice are genetically engineered to express human ACE2 receptors, the same receptors that SARS-CoV-2 targets to infect human cells. By infecting these mice with the virus, scientists can closely study the progression of the disease and its impact on brain function.
 
Key Findings from the Research
-Upregulation of Inflammatory Genes
One of the most significant findings of the study was the substantial upregulation of genes associated with inflammation in the brains of SARS-CoV-2-infected mice. These genes are integral to pathways that lead to the production of cytokines and chemokines, which are proteins that promote and regulate inflammation.

Notable Upregulated Genes:
 
-Cxcl10: This gene showed a dramatic increase in expression, rising over 1300-fold by day six post-infection. Cxcl10 encodes a protein known as IP-10, which plays a role in recruiting immune cells to sites of infection and inflammation.
 
-Ccl2: Also known as MCP-1, this gene was upregulated over 651-fold. Ccl2 is crucial for attracting monocytes, memory T cells, and dendritic cells to sites of tissue injury and infection.
 
-Ccl5 (RANTES): This gene saw a 328-fold increase in expression. Ccl5 is involved in the inflammatory response and has a significa nt role in immune cell trafficking.
 
-Ccl3 (MIP-1α): With an increase of more than 126-fold, Ccl3 contributes to the inflammatory response by promoting the migration and activation of immune cells.
 
-Cxcl9 (MIG): This gene was upregulated 186-fold, and it is important for the immune response, particularly in the recruitment of T cells.
 
These upregulated genes indicate a robust inflammatory response in the brain following SARS-CoV-2 infection, potentially leading to neuroinflammation and subsequent neurological symptoms.
 
-Activation of Cell Death Pathways
The study also identified the upregulation of genes involved in various cell death pathways, including pyroptosis and necroptosis. These forms of cell death can release inflammatory molecules, exacerbating neuroinflammation and contributing to brain damage.
 
Key Upregulated Genes in Cell Death Pathways:
 
-Zbp1: This gene is involved in the regulation of programmed cell death pathways like necroptosis, which can lead to cell lysis and inflammation.
 
-Casp1, Casp7, Casp8: These caspase genes are crucial for the execution of apoptosis and pyroptosis, contributing to the inflammatory response and cell death.
 
Downregulation of Synaptic Signaling Genes
In contrast to the upregulation of inflammatory genes, the study found that genes involved in synaptic signaling and neuronal functions were downregulated. This downregulation could impair brain function and contribute to the neurological symptoms observed in COVID-19 patients.
 
Notable Downregulated Genes:
 
-Gria4, Grin2b, Grm2, Grm3: These genes are part of the glutamatergic synapse signaling pathway, crucial for excitatory neurotransmission in the brain. Their downregulation suggests impaired synaptic function and potential cognitive deficits.
 
-BDNF (Brain-Derived Neurotrophic Factor): This gene supports neuron survival and growth. Its downregulation could contribute to the neurodegenerative effects observed in COVID-19 patients.
 
-Reln (Reelin): This gene plays a critical role in neural migration and positioning in the developing brain. Downregulation of Reln can affect brain development and function.
 
Implications for Long-Term Neurological Health
The significant upregulation of neuroinflammation-associated genes, coupled with the downregulation of synaptic signaling genes, suggests that COVID-19 can have profound long-term effects on brain health. These genetic changes could lead to persistent inflammation and neurological issues, even after the acute phase of the infection has resolved.
 
Potential Treatments and Future Research
Understanding the molecular pathways involved in COVID-19-induced neuroinflammation opens up possibilities for targeted treatments. For instance, drugs that inhibit specific inflammatory pathways could potentially reduce neuroinflammation and mitigate long-term neurological damage.

Future Research Directions:
-TLR2-Targeting Drugs: Since TLR2 pathways are significantly involved in neuroinflammation, researching drugs that target TLR2 could be beneficial in treating COVID-19-induced neurological symptoms.
 
-Neuroprotective Therapies: Developing therapies aimed at protecting neuronal function and preventing synaptic dysfunction could help in managing long-term neurological effects of COVID-19.
 
Conclusion
This study sheds light on the profound impact of COVID-19 on the brain, emphasizing the need for further research into its long-term neurological effects. The upregulation of neuroinflammation-associated genes and the downregulation of synaptic signaling genes highlight the complex interplay between the immune response and brain function in COVID-19. As new variants of SARS-CoV-2 continue to emerge, ongoing research will be crucial in developing effective treatments and interventions to protect brain health.
 
What You Can Do
-Stay Informed: Keep up with the latest research on COVID-19 and its effects on the brain.
 
Seek Help: If you experience persistent neurological symptoms after recovering from COVID-19, consult a healthcare professional for proper evaluation and management.
 
Final Thoughts
COVID-19 is more than just a respiratory illness. Its effects on the brain are profound and can lead to long-term health issues. By understanding the mechanisms behind COVID-19-induced neuroinflammation, we can better address the neurological challenges posed by this pandemic and improve outcomes for affected individuals.
 
The study findings were published in the peer reviewed journal: Pathogens.
https://www.mdpi.com/2076-0817/13/7/528
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/the-role-of-mast-cells-in-sars-cov-2-induced-neuroinflammation
 
https://www.thailandmedical.news/news/covid-19-news-chronic-neuroinflammation-and-the-enigma-of-brain-fade-syndrome-in-neurological-diseases