An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption.

H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice

TESORIERO, Chiara;BERTINI, Giuseppe;BENTIVOGLIO FALES, Marina;
2016-01-01

Abstract

An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption.
2016
influenza A virus; lateral hypothalamus; locus coeruleus; noradrenaline; orexin
File in questo prodotto:
File Dimensione Formato  
tesoriero-et-al-2015-h1n1-influenza-virus-induces-narcolepsy-like-sleep-disruption-and-targets-sleep-wake-regulatory.pdf

solo utenti autorizzati

Tipologia: Versione dell'editore
Licenza: Copyright dell'editore
Dimensione 3.73 MB
Formato Adobe PDF
3.73 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
pnas.1521463112.sapp.pdf

solo utenti autorizzati

Descrizione: Supplementary information
Tipologia: Versione dell'editore
Licenza: Copyright dell'editore
Dimensione 11.33 MB
Formato Adobe PDF
11.33 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/11562/933171
Citazioni
  • ???jsp.display-item.citation.pmc??? 31
  • Scopus 70
  • ???jsp.display-item.citation.isi??? 61
social impact