Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice

作者：Mark A. Harrison, Sara L. Morris, Grace A. Rudman, Daniel J. Rittenhouse, Chandler H. Monk, Siva S. V. P. Sakamuri, Md Mehedi Hasan, Mst Shamima Khatun, Hanyun Wang, Lucas P. Garfinkel, Elizabeth B. Norton, Sangku Kim, Jay K. Kolls, S. Michal Jazwinski, Ricardo Mostany, G. Katakam Prasad V, Elizabeth B. Engler-Chiurazzi, Kevin J. Zwezdaryk · 发表于：Brain Behavior and Immunity · 年份：2024 · DOI：10.1016/j.bbi.2023.12.033 · 被引用次数：17 · 研究领域：Cytomegalovirus and herpesvirus research、Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.