Passive transfer of narcolepsy: Anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice

Aviva Katzav, Maria T. Arango, Shaye Kivity, Susumu Tanaka, Gili Givaty, Nancy Agmon-Levin, Makoto Honda, Juan Manuel Anaya, Joab Chapman, Yehuda Shoenfeld

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

40 Citas (Scopus)

Resumen

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy (a sudden weakening of posture muscle tone usually triggered by emotion) caused by the loss of orexin neurons in the hypothalamus. Autoimmune mechanisms are implicated in narcolepsy by increased frequency of specific HLA alleles and the presence of specific autoantibody (anti-Tribbles homolog 2 (TRIB2) antibodies) in the sera of patients with narcolepsy. Presently, we passively transferred narcolepsy to naïve mice by injecting intra-cerebra-ventricularly (ICV) pooled IgG positive for anti-TRIB2 antibodies. Narcolepsy-IgG-injected mice had a loss of the NeuN (neuronal marker), synaptophysin (synaptic marker) and orexin-positive neurons in the lateral hypothalamus area in narcolepsy compared to control-IgG-injected mice and these changes were associated with narcolepsy-like immobility attacks at four weeks post injection and with hyperactivity and long term memory deficits in the staircase and novel object recognition tests. Similar behavioral and cognitive deficits are observed in narcoleptic patients. This is the first report of passive transfer of experimental narcolepsy to naïve mice induced by autoantibodies and supports the autoimmune pathogenesis in narcolepsy.

Idioma originalInglés estadounidense
Páginas (desde-hasta)24-30
Número de páginas7
PublicaciónJournal of Autoimmunity
Volumen45
DOI
EstadoPublicada - sep 2013

All Science Journal Classification (ASJC) codes

  • Inmulogía y alergología
  • Inmunología

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