TY - JOUR
T1 - Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice
AU - Liu, Meng
AU - Thankachan, Stephen
AU - Kaur, Satvinder
AU - Begum, Suraiya
AU - Blanco-Centurion, Carlos
AU - Sakurai, Takeshi
AU - Yanagisawa, Masashi
AU - Neve, Rachael
AU - Shiromani, Priyattam J.
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Cataplexy
KW - Gene delivery
KW - Herpes simplex virus
KW - Hypocretin
KW - Narcolepsy
KW - Orexin
UR - http://www.scopus.com/inward/record.url?scp=53149147775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53149147775&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2008.06446.x
DO - 10.1111/j.1460-9568.2008.06446.x
M3 - Article
C2 - 18973565
AN - SCOPUS:53149147775
SN - 0953-816X
VL - 28
SP - 1382
EP - 1393
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 7
ER -