ResearchIn-Press PreviewCOVID-19Neuroscience
Open Access | 10.1172/jci.insight.179068
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by McMahon, C. in: JCI | PubMed | Google Scholar
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by Hurley, E. in: JCI | PubMed | Google Scholar
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by Muniz Perez, A. in: JCI | PubMed | Google Scholar
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by Estrada, M. in: JCI | PubMed | Google Scholar
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by Lodge, D. in: JCI | PubMed | Google Scholar
1Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, United States of America
2Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, San Antonio, United States of America
Find articles by Hsieh, J. in: JCI | PubMed | Google Scholar
Published May 23, 2024 - More info
Prenatal exposure to viral pathogens has been known to cause the development of neuropsychiatric disorders in adulthood. Furthermore, COVID-19 has been associated with a variety of neurological manifestations, raising the question of whether in utero SARS-CoV-2 exposure can affect neurodevelopment, resulting in long-lasting behavioral and cognitive deficits. Using a human ACE-2-knock-in mouse model, we have previously shown that prenatal exposure to SARS-CoV-2 at later stages of development leads to fetal brain infection and gliosis in the hippocampus and cortex. In this study, we aimed to determine if infection of the fetal brain results in long-term neuroanatomical alterations of the cortex and hippocampus, as well as any cognitive deficits in adulthood. Here, we show that infected mice developed slower and weighed less in adulthood. We also found altered hippocampal and amygdala volume and aberrant newborn neuron morphology in the hippocampus of adult mice infected in utero. Furthermore, we observed sex-dependent alterations in anxiety-like behavior and locomotion, as well as hippocampal-dependent spatial memory. Taken together, our study revealed long-lasting neurological and cognitive changes as a result of prenatal SARS-CoV-2 infection, identifying a window for early intervention and highlighting the importance of immunization and antiviral intervention in pregnant women.