Analysis of ALS-related proteins during herpes simplex virus-2 latent infection
| Autor: | Jorge Rubén Cabrera, Ignacio Rodriguez-Izquierdo, Jose L. Jimenez, María Ángeles Muñoz-Fernández |
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| Rok vydání: | 2020 |
| Předmět: |
Nervous system
Herpesvirus 2 Human Immunology C9ORF72 Herpes simplex virus Biology medicine.disease_cause lcsh:RC346-429 Mice Cellular and Molecular Neuroscience C9orf72 medicine Animals Neurodegeneration Amyotrophic lateral sclerosis lcsh:Neurology. Diseases of the nervous system Neuroinflammation Mice Inbred BALB C Spinal cord Herpes Genitalis C9orf72 Protein Microglia Research General Neuroscience Amyotrophic Lateral Sclerosis medicine.disease Disease Models Animal medicine.anatomical_structure Neurology Vagina Latency Latent Infection Female ALS |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-15 (2020) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/s12974-020-02044-4 |
| Popis: | BackgroundGenetics have provided hints on potential molecular pathways involved in neurodegenerative diseases (NDD). However, the number of cases caused exclusively by genetic alterations is low, suggesting an important contribution of environmental factors to NDDs. Among these factors, viruses like herpes simplex viruses (HSV-2), capable of establishing lifelong infections within the nervous system (NS), are being proposed to have a role in NDDs. Despite promising data, there is a significant lack of knowledge on this and an urgent need for more research.MethodsWe have set up a mouse model to study HSV latency and its associated neuroinflammation in the spinal cord. The goal of this model was to observe neuroinflammatory changes caused by HSV latent infections, and if those changes were similar to alterations observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients.ResultsIn infected spinal cords, we have observed a strong leukocyte infiltration and a severe alteration of microglia close to motor neurons. We have also analyzed ALS-related proteins: we have not found changes in TDP-43 and Fus in neurons, but interestingly, we have found decreased protein levels of C9orf72, of which coding gene is severely altered in some familial forms of ALS and is critical for microglia homeostasis.ConclusionsLatent infection of HSV in the spinal cord showed altered microglia and leukocyte infiltration. These inflammatory features resembled to those observed in the spinal cord of ALS patients. No changes mimicking ALS neuropathology, such as TDP-43 cytoplasmic inclusions, were found in infected spinal cords, but a decrease in protein levels of C9orf72 was observed. Then, further studies should be required to determine whether HSV-2 has a role in ALS. |
| Databáze: | OpenAIRE |
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