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Recent findings made by the center are highlighted, together with a brief explanation. For pdf files, please go to the publications section on this site.
Dauvilliers Y, Montplaisir J, Cochen V, Desautels A, Einen M, Lin L, Kawashima M, Bayard S, Monaca C, Tiberge M, Filipini D, Tripathy A, Nguyen BH, Kotagal S, Mignot E. Post-H1N1 Narcolepsy-Cataplexy Sleep 2010 33(11):1428-30. Following the H1N1 (swine flu) outbreak of 2010, researchers in Europe, Canada and the United States noted an apparent increase in new narcolepsy cases. This letter to the Editor of Sleep suggests that exposure H1N1 vaccine containing adjuvant ASO3 (used in Europe, not the United States) or infection with H1N1 virus, may trigger narcolepsy in rare cases, and suggests the need for systematic study and replication. Published in Sleep, November 1, 2010.
Kawashima M, Lin L, Tanaka S, Jennum P, Knudsen S, Nevsimalova S, Plazzi G, Mignot E. Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy. Sleep. 2010 33(7):869-74. This study extends upon a previous report by Cvetkovic-Lopes identifying autoantibodies directed against the TRIB2 protein in Narcolepsy cases. Here, autoantibodies were found to be present more often in narcolepsy cases only close to disease onset, and rarely found in cases without cataplexy, or long after disease onset. Published in Sleep July 1, 2010.
Aran A, Lin L. Nevsimalova S, Plazzi G, Hong SC, Weiner K, Zeitzer J, Mignot E. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 2009 32:979-983. Markers indicating recent Streptococcal infections were elevated in narcolepsy cases close to disease onset. This suggests that Streptococcal infections may play a role in triggering the onset of the disease. Published in Sleep, August 1, 2009.
Hallmayer J, Faraco J, Lin L, Hesselson S, Winklemann J, Kawashima M, Mayer G, Plazzi G, Nevsimalova S, Bourgin P, Hong S, Honda Y, Honda M, Högl B, Longstreth Jr WT, Montplaisir J, Kemlink D, Einen M, Chen J, Musone SL, Akana M, Miyagawa T, Duan J, Desautels A, Erhardt C, Hesla PE, Poll F, Frauscher B, Jeong JH, Sung-Pil Lee SP, Ton TGN, Kvale M, Kolesar LB, Dobrovolna M, Nepom GT, Salomon D, Wichmann HE, Rouleau GA, Gieger C, Levinson DF, Gejman PV, Meitinger T, Young T, Peppard P, Tokunaga K, Kwock PY, Risch N, Mignot E. Narcolepsy is strongly associated with the TCR alpha locus. Nature Genet, 41(6):708-11 This genome wide association demonstrated that variants at the T cell receptor alpha locus are associated with susceptibility to narcolepsy across ethnic groups. These findings provide strong evidence for an autoimmune pathology in the disease. Published in Nature Genetics, June 2009.
Yokogawa T, Marin W, Faraco J, Pezeron G, Appelbaum L, Rosa F, Mourrain P, Mignot E. Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol. 2007, Oct 16;5(10):e277. This report established that zebrafish, a widely used vertebrate model organism, display sleep behaviors and have a functional hypocretin neuropeptide system. Unlike in mammals, however, hypocretin neurons interact with different cell types in the fish, and act to promote sleep rather than wakefulness. Hypocretins in fish act to consolodate sleep in fish as they do in mammals, and fish without hypocretin receptors have disrupted sleep as seen in narcolepsy in humans, rodents and dogs. Published in Public Library of Science, Biology, October 16, 2007.
Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, Vankova J, Black J, Harsh J, Bassetti C, Schrader H, Nishino S. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol., 59(10): 1553-1562. This large study established the use of CSF hypocretin measurement as a diagnostic tool for narcolepsy, with levels below 110pg/mL being diagnostic. Published in The Archives of Neurology, October 2002.
Mignot E, Lin L, Rogers W, Honda Y, Qiu X, Lin X, Okun M, Hohjoh H, Miki T, Hsu S, Leffell M, Grumet F, Fernandez-Vina M, Honda M, Risch N. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet 2001 Mar;68(3):686-99. American Journal of Human Genetics, March 1st, 2001. The first systematic HLA study on narcolepsy across three different ethnic groups.
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999 Aug 6;98(3):365-76.
Canine narcolepsy is caused by mutations in the hypocretin (orexin) receptor 2 gene. First publication implicating the hypocretin system in narcolepsy, published in Cell August 6th, 1999.
Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E.Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000 Jan 1;355(9197):39-40
Human narcolepsy is associated with undetectable hypocretin-1 levels in the cerebrospinal fluid. First publication implicating the hypocretin system in human narcolepsy, published in The Lancet, January 1st 2000.
Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000 Sep;6(9):991-7.
Most cases of human narcolepsy cases are not caused by hypocretin gene mutations. Only one hypocretin mutation was found, in a case with unsually early narcolepsy onset at 6 months of age. This finding demonstrates that hypocretin mutations can cause narcolepsy in humans as they do in animals.
This manuscript also extends on the human CSF study by showing that human narcolepsy brain tissues have no hypocretin-1 and 2 peptides. It also reports that human narcolepsy cases have no preprohypocretin transcripts in their hypothalami, an area containing the hypocretin cells. First publication indicating that human narcolepsy is caused by a destruction of hypocretin-containing cells, published in Nature Medicine, September 1st 2000.
