ADVERTISEMENT
CURRENT ISSUE
DECEMBER 2014
KINDLE EDITION



SEARCH JOURNAL ARCHIVES


SEARCH PUBMED


MANUSCRIPT SUBMISSIONS


SUBSCRIBE TO SLEEP

CONTINUING MEDICAL EDUCATION


ADVERTISE WITH US


ABOUT SLEEP

ABSTRACT SUPPLEMENTS


ACCEPTED PAPERS
Bookmark and Share         RSS Feed

VOLUME 36, ISSUE 01

EFFECTS OF OREXIN GENE TRANSFER IN OREXIN KNOCKOUT MICE
Effects of Orexin Gene Transfer in the Dorsolateral Pons in Orexin Knockout Mice

http://dx.doi.org/10.5665/sleep.2296

Carlos Blanco-Centurion, PhD2; Meng Liu, PhD2; RodaRani Konadhode, PhD2; Dheeraj Pelluru, PhD2; Priyattam J. Shiromani, PhD1,2

1Ralph H. Johnson VA Medical Center, Charleston, SC; 2Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC



  Expand  Table of Contents    
Text size:  

Study Objectives:

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.

Design:

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.

Measurements and 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.

Conclusion:

Orexin gene transfer into the dorsolateral pontine neurons can control cataplexy attacks and modestly improve wake maintenance.

Citation:

Blanco-Centurion C; Liu M; Konadhode R; Pelluru D; Shiromani PJ. Effects of orexin gene transfer in the dorsolateral pons in orexin knockout mice. SLEEP 2013;36(1):31–40.

Expand  Table of Contents
ADVERTISEMENT
Classifieds View SLEEP 2011 Poster Presentations Online