title: Effects of orexin gene transfer in the dorsolateral pons in orexin knockout mice.
abstract: OBJECTIVE
  Narcolepsy is a sleep disorder characterized by loss of orexin neurons. Previously, our group demonstrated that transfer of the orexin gene into surrogate neurons in the lateral hypothalamus and the zona incerta significantly reduced cataplexy bouts in the orexin-ataxin-3 mice model of narcolepsy. The current study determined the effects of orexin gene transfer into the dorsolateral pontine neurons in the orexin knockout (KO) mice model of narcolepsy. The dorsolateral pons was chosen because it plays a critical role in regulating muscle tone and thus it is conceivable to be involved in cataplexy as well. Cataplexy is the pathognomonic symptom in narcolepsy.
  
  
  METHODS
  Independent groups of orexin KO mice were given bilateral microinjections (0.75 μL each side) of either recombinant adenoassociated virus-orexin (rAAV-orexin; n = 7), or rAAV-green fluorescent protein (rAAV-GFP; n = 7) into the dorsolateral pons. A group of orexin KO mice that did not receive rAAV (n = 7) and a group of wild-type mice (C57BL/J6; n = 5) were used as controls. Three weeks after rAAV-mediated gene transfer narcolepsy symptoms were examined using sleep and behavioral recordings. Number, location of the orexin-immunoreactive neurons, and relative density of orexin immunoreactive fibers were determined.
  
  
  RESULTS
  Orexin gene transfer into the dorsolateral pons significantly decreased cataplexy and modestly improved wake maintenance compared to the orexin KO mice that did not receive rAAV. In contrast, GFP gene transfer worsened narcoleptic symptoms compared to the no-rAAV orexin KO group.
  
  
  CONCLUSIONS
  Orexin gene transfer into the dorsolateral pontine neurons can control cataplexy attacks and modestly improve wake maintenance.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Blanco-Centurion
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: RodaRani
authors.initials: R
authors.lastname: Konadhode
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Pelluru
authors.forename: Priyattam J
authors.initials: PJ
authors.lastname: Shiromani
mesh_terms: D000818:Animals; D002385:Cataplexy / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005260:Female; D018014:Gene Transfer Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009290:Narcolepsy / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D000068797:Orexins; D011149:Pons / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins