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

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 s...

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Autores:
Tipo de recurso:
Fecha de publicación:
2013
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22254
Acceso en línea:
https://doi.org/10.1016/j.jaut.2013.06.010
https://repository.urosario.edu.co/handle/10336/22254
Palabra clave:
Autoantibody
Biological marker
Hla antibody
Immunoglobulin g
Neuron specific nuclear protein
Orexin
Synaptophysin
Trib2 autoantibody
Unclassified drug
Animal experiment
Animal model
Animal tissue
Article
Autoimmunity
Brain region
Cataplexy
Cognitive defect
Controlled study
Daytime somnolence
Human
Hyperactivity
Hypothalamus
Immobilization
Long term memory
Mouse
Narcolepsy
Nonhuman
Normal human
Passive transport
Pathogenesis
Priority journal
Recognition
Sleep
Anti-tribbles homolog 2 (trib2) antibodies
Behavioral deficits
Narcolepsy
Orexin
Passive transfer
Animals
Autoantibodies
Autoantigens
Cataplexy
Cell death
Female
Humans
Hypothalamus
Immunoglobulin g
Intracellular signaling peptides and proteins
Mice
Narcolepsy
Neurons
Neuropeptides
Anti-tribbles homolog 2 (trib2) antibodies
Behavioral deficits
Narcolepsy
Orexin
Passive transfer
passive
inbred c3h
animal
physiological
Disease models
Immunization
Mice
Pattern recognition
Rights
License
Abierto (Texto Completo)
Description
Summary: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.