SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons
An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestat...
| Main Authors: | , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Elsevier
2023-12-01
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| Colecção: | Experimental and Molecular Pathology |
| Assuntos: | |
| Acesso em linha: | http://www.sciencedirect.com/science/article/pii/S0014480023000254 |
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| author | G. Cappelletti E.V. Carsana G. Lunghi S. Breviario C. Vanetti A.B. Di Fonzo E. Frattini M. Magni S. Zecchini M. Clerici M. Aureli C. Fenizia |
| author_facet | G. Cappelletti E.V. Carsana G. Lunghi S. Breviario C. Vanetti A.B. Di Fonzo E. Frattini M. Magni S. Zecchini M. Clerici M. Aureli C. Fenizia |
| author_sort | G. Cappelletti |
| collection | DOAJ |
| description | An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far.To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers.These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested. |
| first_indexed | 2024-03-08T23:14:45Z |
| format | Article |
| id | doaj.art-c66e11f63d4e429fb51a1a7d9a0f2381 |
| institution | Directory Open Access Journal |
| issn | 1096-0945 |
| language | English |
| last_indexed | 2024-03-08T23:14:45Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental and Molecular Pathology |
| spelling | doaj.art-c66e11f63d4e429fb51a1a7d9a0f23812023-12-15T07:21:48ZengElsevierExperimental and Molecular Pathology1096-09452023-12-01134104874SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neuronsG. Cappelletti0E.V. Carsana1G. Lunghi2S. Breviario3C. Vanetti4A.B. Di Fonzo5E. Frattini6M. Magni7S. Zecchini8M. Clerici9M. Aureli10C. Fenizia11Department of Biomedical and Clinical Sciences, University of Milan, via G.B. Grassi 74, 20157 Milan, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, via F.lli Cervi 93, 20054 Segrate, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, via F.lli Cervi 93, 20054 Segrate, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, via F.lli Cervi 93, 20054 Segrate, ItalyDepartment of Biomedical and Clinical Sciences, University of Milan, via G.B. Grassi 74, 20157 Milan, ItalyIRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, ItalyIRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, ItalyIRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences, University of Milan, via G.B. Grassi 74, 20157 Milan, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, Italy; IRCCS Fondazione Don Gnocchi, via Capecelatro 66, 20148 Milan, ItalyDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, via F.lli Cervi 93, 20054 Segrate, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, Italy; Corresponding author at: Department of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, Italy.An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far.To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers.These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.http://www.sciencedirect.com/science/article/pii/S0014480023000254SARS-CoV-2 infectionDopaminergic neuronsPost COVIDDopamineNeuronal stressSARS-CoV-2 variants |
| spellingShingle | G. Cappelletti E.V. Carsana G. Lunghi S. Breviario C. Vanetti A.B. Di Fonzo E. Frattini M. Magni S. Zecchini M. Clerici M. Aureli C. Fenizia SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons Experimental and Molecular Pathology SARS-CoV-2 infection Dopaminergic neurons Post COVID Dopamine Neuronal stress SARS-CoV-2 variants |
| title | SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons |
| title_full | SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons |
| title_fullStr | SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons |
| title_full_unstemmed | SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons |
| title_short | SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons |
| title_sort | sars cov 2 hampers dopamine production in ipsc derived dopaminergic neurons |
| topic | SARS-CoV-2 infection Dopaminergic neurons Post COVID Dopamine Neuronal stress SARS-CoV-2 variants |
| url | http://www.sciencedirect.com/science/article/pii/S0014480023000254 |
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