S.T. and S.K. contributed equally to the project.
Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice
Version of Record online: 29 SEP 2008
© The Authors (2008). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 28, Issue 7, pages 1382–1393, October 2008
How to Cite
Liu, M., Thankachan, S., Kaur, S., Begum, S., Blanco-Centurion, C., Sakurai, T., Yanagisawa, M., Neve, R. and Shiromani, P. J. (2008), Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice. European Journal of Neuroscience, 28: 1382–1393. doi: 10.1111/j.1460-9568.2008.06446.x
- Issue online: 1 OCT 2008
- Version of Record online: 29 SEP 2008
- Received 19 May 2008, revised 5 August 2008, accepted 7 August 2008
- gene delivery;
- herpes simplex virus;
Gene transfer has proven to be an effective neurobiological tool in a number of neurodegenerative diseases, but it is not known if it can correct a sleep disorder. Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Here, a replication-defective herpes simplex virus-1 amplicon-based vector was constructed to transfer the gene for mouse prepro-orexin into mice with a genetic deletion of the orexin gene. After in vitro tests confirmed successful gene transfer into cells, the gene vector was delivered to the lateral hypothalamus of orexin knockout (KO) mice where the orexin peptide was robustly expressed in the somata and processes of numerous neurons, and the peptide product was detected in the cerebrospinal fluid. During the 4-day life-span of the vector the incidence of cataplexy declined by 60%, and the levels of rapid eye movement sleep during the second half of the night were similar to levels in wild-type mice, indicating that narcoleptic sleep–wake behavior in orexin KO mice can be improved by targeted gene transfer.