SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation.
Qian GeShan ZhouJose PorrasPanfeng FuTing WangJianyang DuKun LiPublished in: bioRxiv : the preprint server for biology (2023)
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of "long COVID" neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y MA30 , we demonstrated that intranasal inoculation of SARS2-N501Y MA30 results in viral dissemination to multiple brain regions, including the amygdala and hippocampus. Behavioral assays show a significant increase in anxiety- and depression-like behaviors 14 days following viral infection. Moreover, we observed microglia activation following SARS2-N501Y MA30 infection, along with an augmentation in microglia-dependent neuronal activity in the amygdala. Pharmacological inhibition of microglial activity subsequent to viral spike inoculation mitigates microglia-dependent neuronal hyperactivity. Furthermore, transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating microglia-driven neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Overall, these data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- inflammatory response
- neuropathic pain
- cerebral ischemia
- coronavirus disease
- lipopolysaccharide induced
- lps induced
- functional connectivity
- resting state
- high glucose
- subarachnoid hemorrhage
- spinal cord
- single cell
- blood brain barrier
- poor prognosis
- machine learning
- physical activity
- cognitive impairment
- white matter
- deep learning
- endothelial cells
- sleep quality