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 RevistaArtículo

39 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. © 2013 Elsevier Ltd.
Idioma originalEnglish (US)
Páginas (desde-hasta)24-30
Número de páginas7
PublicaciónJournal of Autoimmunity
DOI
EstadoPublished - sep 1 2013

Huella dactilar

Narcolepsy
Autoantibodies
Sleep
Immunoglobulin G
Neurons
Cataplexy
Lateral Hypothalamic Area
Transfer (Psychology)
Synaptophysin
Long-Term Memory
Antibodies
Memory Disorders
Cerebrum
Posture
Hypothalamus
Emotions
Alleles
Muscles
Injections

Citar esto

Katzav, Aviva ; Arango, Maria T. ; Kivity, Shaye ; Tanaka, Susumu ; Givaty, Gili ; Agmon-Levin, Nancy ; Honda, Makoto ; Anaya, Juan Manuel ; Chapman, Joab ; Shoenfeld, Yehuda. / Passive transfer of narcolepsy: Anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice. En: Journal of Autoimmunity. 2013 ; pp. 24-30.
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title = "Passive transfer of narcolepsy: Anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice",
abstract = "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 na{\"i}ve 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 na{\"i}ve mice induced by autoantibodies and supports the autoimmune pathogenesis in narcolepsy. {\circledC} 2013 Elsevier Ltd.",
author = "Aviva Katzav and Arango, {Maria T.} and Shaye Kivity and Susumu Tanaka and Gili Givaty and Nancy Agmon-Levin and Makoto Honda and Anaya, {Juan Manuel} and Joab Chapman and Yehuda Shoenfeld",
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Passive transfer of narcolepsy: Anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice. / Katzav, Aviva; Arango, Maria T.; Kivity, Shaye; Tanaka, Susumu; Givaty, Gili; Agmon-Levin, Nancy; Honda, Makoto; Anaya, Juan Manuel; Chapman, Joab; Shoenfeld, Yehuda.

En: Journal of Autoimmunity, 01.09.2013, p. 24-30.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Passive transfer of narcolepsy: Anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice

AU - Katzav, Aviva

AU - Arango, Maria T.

AU - Kivity, Shaye

AU - Tanaka, Susumu

AU - Givaty, Gili

AU - Agmon-Levin, Nancy

AU - Honda, Makoto

AU - Anaya, Juan Manuel

AU - Chapman, Joab

AU - Shoenfeld, Yehuda

PY - 2013/9/1

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N2 - 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. © 2013 Elsevier Ltd.

AB - 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. © 2013 Elsevier Ltd.

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