A work has presented results related to the development of a new cellular model that allows studying the connections between infection by the herpes simplex virus 1 (HSV-1), which causes lesions in the oral mucosa, and Alzheimer's disease, most common form of dementia.

The proposal of the possible involvement of the virus in the development of this neurodegenerative disease is framed in the infectious hypothesis of Alzheimer's, which maintains that infection by certain pathogens could contribute, in various ways, to the neurodegeneration typical of the disease.

In this context, HSV-1 is one of the most studied candidates due to its high prevalence in the population and its ability to settle long-term in the cells of the nervous system.

The results, published in the journal Microorganisms , are signed by the group led by Dr. María Jesús Bullido, professor at the Autonomous University of Madrid (UAM) at the "Severo Ochoa" Molecular Biology Center (CBMSO, CSIC-UAM). .

HSV-1 virus and ReN cells

There are numerous studies that support the possible association between the HSV-1 virus and Alzheimer's-type neurodegeneration, the confirmation of which could lead to the search for new preventive and therapeutic strategies against such a high-impact disease.

Recently, Dr. Bullido's laboratory, which has been studying the effects of HSV-1 infection on Alzheimer's for years, has redirected its research to work with the ReNcell VM cell line.

ReN cells are human neuronal progenitors, cells capable of dividing and, under certain conditions, specializing and generating different types of cells present in the human central nervous system through a process called cellular differentiation.

The authors induced the differentiation of these cells, giving rise to heterogeneous cultures composed not only of neurons but also of glial cells, which serve as support and play a key role in the progression of Alzheimer's disease.

“This characteristic of ReN cells makes them especially interesting in the development of new models of infection and neurodegeneration, since it allows us to study the effects of HSV-1 considering the interactions established between different types of cells present in the human nervous system” , explain the researchers.

Towards a better understanding of the disease

The researchers' main objective was to determine the usefulness of these cells to study the relationships between HSV-1 and Alzheimer's. After confirming that the ReN cell cultures, differentiated or not, could be infected by the virus, they proceeded to reproduce some of the experiments previously carried out with other cell lines.

They observed various alterations associated with Alzheimer's, such as the intracellular accumulation of the beta-amyloid peptide and the hyperphosphorylated tau protein, distinctive features of this disease, and alterations in the "cellular recycling" mechanisms, known as the autophagy-lysosomal pathway, which also They are strongly related to the pathology of Alzheimer's.

Together, their results support the use of this cell line in the development of new platforms to further study the connections between HSV-1 infection and Alzheimer's-type neurodegeneration.

Among the team's future perspectives is the characterization of other alterations associated with infection, such as changes in cholesterol metabolism or neuroinflammation, as well as the development of more complex three-dimensional models.

“These would not only maintain the cellular diversity that we have highlighted before, but would also reproduce a structure more similar to that found in the human brain, which would allow a better understanding of what happens when we get sick,” the authors detail.

In conclusion, given the difficulties involved in studying the nervous system, as well as the technical and ethical limitations of the models used until now to address the problem of Alzheimer's, it is essential to search for alternatives such as the one presented in this study.

“Working on the development of models that, by better reproducing the environment of the human brain, allows us to better understand the enigmas it entails, both in health and disease, is a priority,” the authors conclude.

_____________________

Image: On the left, a photograph taken with the phase contrast microscope of a differentiated culture of ReN cells. You can see the characteristic extensions of the cells of the nervous system. On the right, an immunofluorescence image of a differentiated ReN cell culture infected by HSV-1. The nuclei of the cells are seen in blue, while a viral protein is marked in red, indicating that most of the cells are infected. Finally, you can see, in green, one of the alterations associated with Alzheimer's disease and induced by the virus: the accumulation of beta-amyloid peptide inside infected cells. / Blanca Salgado

Bibliographic reference: Salgado, B.; Tailor, I.; Bullido, MJ; Aldudo, J. (2023). Herpes Simplex Virus Type 1 Induces AD-like Neurodegeneration Markers in Human Progenitor and Differentiated ReNcell VM Cells . Microorganisms , 11, 1205. Doi.org/10.3390/microorganisms11051205

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