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.

SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons / 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. - In: EXPERIMENTAL AND MOLECULAR PATHOLOGY. - ISSN 0014-4800. - 134:(2023 Dec), pp. 104874.1-104874.9. [Epub ahead of print] [10.1016/j.yexmp.2023.104874]

SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons

G. Cappelletti
Co-primo
;
E.V. Carsana
Co-primo
;
G. Lunghi
Co-primo
;
S. Breviario;C. Vanetti;E. Frattini;S. Zecchini;M. Clerici;M. Aureli
Co-ultimo
;
C. Fenizia
Co-ultimo
2023

Abstract

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.
Dopamine; Dopaminergic neurons; Neuronal stress; Post COVID; SARS-CoV-2 infection; SARS-CoV-2 variants
Settore MED/04 - Patologia Generale
Settore BIO/13 - Biologia Applicata
Settore BIO/10 - Biochimica
   One Health Basic and Translational Research Actions addressing Unmet Need on Emerging Infectious Diseases (INF-ACT)
   INF-ACT
   MINISTERO DELL'UNIVERSITA' E DELLA RICERCA
   PE00000007
dic-2023
30-set-2023
https://www.sciencedirect.com/science/article/pii/S0014480023000254?via=ihub
Article (author)
File in questo prodotto:
File Dimensione Formato  
SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons.pdf

accesso aperto

Descrizione: Article
Tipologia: Publisher's version/PDF
Dimensione 2.28 MB
Formato Adobe PDF
2.28 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1005918
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 1
social impact