好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Loss of Orexine Neurons in the Hypothalamus and Narcolepsy-Like Behavior Induced by Autoantibodies in Mice
Sleep
S19 - (-)
003
Narcolepsy is a sleep disorder characterized by abrupt attacks of somnolence caused by the loss of orexine 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 protein antibodies) in the sera of narcolepsy patients.
We examined behavior and brain pathology of naive C3H mice injected intra-cerebra-ventricularly (ICV) with pooled IgG from narcolepsy patients positive for anti-Trib2. Control mice were injected with pooled matched healthy control IgG. Mice were filmed and analyzed for immobility attacks weekly before and after ICV injection by using Noldus PhenoTyper cage and EthVision software. Mice were also examined for behavior and cognition in the staircase, novel object recognition and Y-maze tests. Brains were removed and analyzed by immunofluorescence for neurodegeneration in the hypothalamus.
We found loss of neuronal marker (NeuN) and synaptic marker (synaptophysin) staining in the lateral hypothalamus area in narcolepsy-injected mice compared to controls. A specific loss of orexine-positive neurons in narcolepsy-IgG was found. We observed narcolepsy-like immobility attacks in narcolepsy injected mice 4 weeks post injection but not before. We found that narcolepsy-injected mice were significantly hyperactive in the staircase test and had significant short memory deficits in the Y-maze test compared to controls. The behavioral and cognitive results are similar to those observed in line narcolepsy patients.
This is the first report of passive transfer experimental narcolepsy induced by autoantibodies and supports an autoimmune pathogenesis of narcolepsy.
Authors/Disclosures
Aviva Katzav, PhD (Sheba Medical Center, Neurology)
PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
Joab Chapman, MD, PhD (Sheba Medical Center) Dr. Chapman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mapi Pharma. Dr. Chapman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Chapman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk Serono. The institution of Dr. Chapman has received research support from Ministry Of Industry.
No disclosure on file
No disclosure on file
No disclosure on file
James D. Berry, MD MPH (Massachusetts General Hospital) Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene Nanomedicine. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma Holdings of America. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berry has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Berry has stock in ReactNeuro. The institution of Dr. Berry has received research support from Biogen. The institution of Dr. Berry has received research support from MT Pharma of America. The institution of Dr. Berry has received research support from Rapa Therapeutics. The institution of Dr. Berry has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Berry has received research support from Alexion. The institution of Dr. Berry has received research support from nQ Medical. The institution of Dr. Berry has received research support from ALSA. The institution of Dr. Berry has received research support from MDA. The institution of Dr. Berry has received research support from Amylyx. The institution of Dr. Berry has received research support from Transposon. Dr. Berry has a non-compensated relationship as a Scientific Advisor with Everything ALS that is relevant to AAN interests or activities.
No disclosure on file