tetano
Editor, Senior Moderator
Nat Aging
. 2024 Nov;4(11):1598-1618.
doi: 10.1038/s43587-024-00730-z. Epub 2024 Nov 14. Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection
Ting Zhang[SUP] 1 2 3 4 [/SUP], Yunfeng Li[SUP] 5 [/SUP], Liuliu Pan[SUP] 6 7 [/SUP], Jihui Sha[SUP] 8 [/SUP], Michael Bailey[SUP] 9 [/SUP], Emmanuelle Faure-Kumar[SUP] 10 [/SUP], Christopher Kazu Williams[SUP] 1 2 [/SUP], James Wohlschlegel[SUP] 8 11 [/SUP], Shino Magaki[SUP] 1 12 [/SUP], Chao Niu[SUP] 13 [/SUP], Yoojin Lee[SUP] 13 [/SUP], Yu-Chyuan Su[SUP] 13 [/SUP], Xinmin Li[SUP] 12 13 [/SUP], Harry V Vinters[SUP] 14 15 16 [/SUP], Daniel H Geschwind[SUP] 17 18 19 20 [/SUP]
Affiliations
Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.
. 2024 Nov;4(11):1598-1618.
doi: 10.1038/s43587-024-00730-z. Epub 2024 Nov 14. Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection
Ting Zhang[SUP] 1 2 3 4 [/SUP], Yunfeng Li[SUP] 5 [/SUP], Liuliu Pan[SUP] 6 7 [/SUP], Jihui Sha[SUP] 8 [/SUP], Michael Bailey[SUP] 9 [/SUP], Emmanuelle Faure-Kumar[SUP] 10 [/SUP], Christopher Kazu Williams[SUP] 1 2 [/SUP], James Wohlschlegel[SUP] 8 11 [/SUP], Shino Magaki[SUP] 1 12 [/SUP], Chao Niu[SUP] 13 [/SUP], Yoojin Lee[SUP] 13 [/SUP], Yu-Chyuan Su[SUP] 13 [/SUP], Xinmin Li[SUP] 12 13 [/SUP], Harry V Vinters[SUP] 14 15 16 [/SUP], Daniel H Geschwind[SUP] 17 18 19 20 [/SUP]
Affiliations
- PMID: 39543407
- DOI: 10.1038/s43587-024-00730-z
Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.