Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter
{"title":"SARS-CoV-2感染急性后神经精神和认知后遗症——来自K18-hACE C57BL/6 J小鼠的证据","authors":"Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter","doi":"10.1093/ijnp/pyaf072","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. Using a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC), we examined neurobiological mechanisms underlying these effects without the confounding influence of contextual factors.</p><p><strong>Results: </strong>SARS-CoV-2 infection induced cognitive, but not anxiety- or depression-like, behavioral deficits. Cognitive impairments correlated with severity of the acute disease. Infected mice showed significant alterations in brain cytokine levels, as well as in kynurenine pathway (KP) metabolites, both of which were associated with acute disease severity. Microbiome taxonomic profiling revealed group-specific differences, indicating that certain bacterial species may contribute to PASC development.</p><p><strong>Conclusions: </strong>Our findings suggest that SARS-CoV-2 infection causes cognitive deficits in PASC, modulated by acute disease severity, while anxiety- and depression-like behaviors appear unrelated to the viral infection itself. This supports the idea that such psychiatric symptoms may stem from pandemic-related stressors rather than infection. Altered cytokine signaling and KP metabolism may play key roles in the pathophysiology of PASC, identifying potential biomarkers and therapeutic targets.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542986/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.\",\"authors\":\"Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter\",\"doi\":\"10.1093/ijnp/pyaf072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. Using a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC), we examined neurobiological mechanisms underlying these effects without the confounding influence of contextual factors.</p><p><strong>Results: </strong>SARS-CoV-2 infection induced cognitive, but not anxiety- or depression-like, behavioral deficits. Cognitive impairments correlated with severity of the acute disease. Infected mice showed significant alterations in brain cytokine levels, as well as in kynurenine pathway (KP) metabolites, both of which were associated with acute disease severity. Microbiome taxonomic profiling revealed group-specific differences, indicating that certain bacterial species may contribute to PASC development.</p><p><strong>Conclusions: </strong>Our findings suggest that SARS-CoV-2 infection causes cognitive deficits in PASC, modulated by acute disease severity, while anxiety- and depression-like behaviors appear unrelated to the viral infection itself. This supports the idea that such psychiatric symptoms may stem from pandemic-related stressors rather than infection. Altered cytokine signaling and KP metabolism may play key roles in the pathophysiology of PASC, identifying potential biomarkers and therapeutic targets.</p>\",\"PeriodicalId\":14134,\"journal\":{\"name\":\"International Journal of Neuropsychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542986/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuropsychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ijnp/pyaf072\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyaf072","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.
Background: Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. Using a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC), we examined neurobiological mechanisms underlying these effects without the confounding influence of contextual factors.
Results: SARS-CoV-2 infection induced cognitive, but not anxiety- or depression-like, behavioral deficits. Cognitive impairments correlated with severity of the acute disease. Infected mice showed significant alterations in brain cytokine levels, as well as in kynurenine pathway (KP) metabolites, both of which were associated with acute disease severity. Microbiome taxonomic profiling revealed group-specific differences, indicating that certain bacterial species may contribute to PASC development.
Conclusions: Our findings suggest that SARS-CoV-2 infection causes cognitive deficits in PASC, modulated by acute disease severity, while anxiety- and depression-like behaviors appear unrelated to the viral infection itself. This supports the idea that such psychiatric symptoms may stem from pandemic-related stressors rather than infection. Altered cytokine signaling and KP metabolism may play key roles in the pathophysiology of PASC, identifying potential biomarkers and therapeutic targets.
期刊介绍:
The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.