Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

Autor: Dhuria SV; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Fine JM; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Bingham D; Center for Immunochemistry, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, United States., Svitak AL; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Burns RB; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Baillargeon AM; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Panter SS; Center for Immunochemistry, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, United States., Kazi AN; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Frey WH 2nd; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States., Hanson LR; HealthPartners Institute for Education and Research, Center for Memory and Aging, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, United States. Electronic address: Leah.R.Hanson@HealthPartners.com.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2016 Aug 03; Vol. 627, pp. 155-9. Date of Electronic Publication: 2016 Jun 02.
DOI: 10.1016/j.neulet.2016.05.053
Abstrakt: Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: