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Publication : Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model.

First Author  Fongsaran C Year  2024
Journal  Brain Behav Immun Health Volume  38
Pages  100780 PubMed ID  38706571
Mgi Jnum  J:361153 Mgi Id  MGI:7856005
Doi  10.1016/j.bbih.2024.100780 Citation  Fongsaran C, et al. (2024) Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model. Brain Behav Immun Health 38:100780
abstractText  Alzheimer's disease is classified as a progressive disorder resulting from protein misfolding, also known as proteinopathies. Proteinopathies include synucleinopathies triggered by misfolded amyloid alpha-synuclein, tauopathies triggered by misfolded tau, and amyloidopathies triggered by misfolded amyloid of which Alzheimer's disease (beta-amyloid) is most prevalent. Most neurodegenerative diseases (>90%) are not due to dominantly inherited genetic causes. Instead, it is thought that the risk for disease is a complicated interaction between inherited and environmental risk factors that, with age, drive pathology that ultimately results in neurodegeneration and disease onset. Since it is increasingly appreciated that encephalitic viral infections can have profoundly detrimental neurological consequences long after the acute infection has resolved, we tested the hypothesis that viral encephalitis exacerbates the pathological profile of protein-misfolding diseases. Using a robust, reproducible, and well-characterized mouse model for beta-amyloidosis, Tg2576, we studied the contribution of alphavirus-induced encephalitis (TC-83 strain of VEEV to model alphavirus encephalitis viruses) on the progression of neurodegenerative pathology. We longitudinally evaluated neurological, neurobehavioral, and cognitive levels, followed by a post-mortem analysis of brain pathology focusing on neuroinflammation. We found more severe cognitive deficits and brain pathology in Tg2576 mice inoculated with TC-83 than in their mock controls. These data set the groundwork to investigate sporadic Alzheimer's disease and treatment interventions for this infectious disease risk factor.
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