Progress 07/01/05 to 09/30/09
Outputs
OUTPUTS: These studies documented that orexin induced feeding requires changes in the release of two neurotransmitters, glutamate and gaba, in the perifornical region of the lateral hypothalamus. Furthermore, they confirmed the importance of NMDA receptors in the lateral hypothalamus for orexin-induced feeding. PARTICIPANTS: J.L Beverly, PhD, was Principle Investigator. The research was part of the graduate training for Dolores Doane Guest, PhD, and involved a collaboration with Dr. Katherine Kotz, PhD, University of Minnesota/VA Hospital. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
This research increased our understanding of a key neural pathway involved in initiating feeding and provided novel information necessary to develope new strategies to regulate food intake in domestic animals.
Publications
- Thorpe A.J., Doane, D.F., Sweet, D.C., Beverly, J.L. and Kotz, C.M. 2006. Orexin A in the rostrolateral hypothalamic area induces feeding by modulating GABAergic transmission. Brain Res. 1125(1):60-6.
- Doane, D.F., Lawson, M.A., Meade, J.R., Kotz, C.M. and Beverly, J.L. 2007. Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus. Am. J. Physiol. 293:R1022-6.
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: Our previous studies documented changes in the release of two neurotransmitters, glutamate and gaba, in the perifornical region of the lateral hypothalamus in response to increased local levels of orexin. Those studies came to concentrate on the role of glutamate, via NMDA receptors, on orexin-induced feeding. Current studies are designed to investigate other ionotropic glutamate receptor subtypes, e.g. AMPA and Kainate, in the regions that have been implicated in feeding using the antagonists CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione). Unfortunately, the antagonists alone, at the concentrations tested, may increase food intake independent of Orexin. Studies in the next funding year will concentrate on using lower doses of the antagonists to clearly establish whether these other receptors are important in orexin-induced feeding. If completed in time, a study to evaluate metabotropic glutamate receptors in orexin's feeding response will be initiated. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Unfortunately, the AMPA/KA antagonists chosen may stimulate feeding independent of orexin. Dose-response studies are necessary to clearly establish whether the AMPA/KA receptors mediate some of the feeding response to Orexin. This research will increase our understanding of a key neural pathway involved in initiating feeding and provide novel information to aid in developing new strategies to regulate food intake in domestic animals.
Publications
- No publications reported this period
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: The results from this project were disseminated during this year as a publication in the Regulatory, Integrative and Comparative Physiology section of the American Journal of Physiology.
PARTICIPANTS: J.L. Beverly (PI), Dolores Doane (PhD student), Kristy Heppner (undergraduate student), and Kelli Coleman (a high school student participating in the College of ACES Rap II summer program) contributed to the project this year.
Impacts
The results from this project identified the importance of glutamatergic neural circuits in the lateral hypothalamus in mediating the feeding response to orexinergic neural circuits. Once activated, the orexin-containing neurons in the perifornical region of the hypothalamus stimulate feed consumption. The effect on feeding-related mechanisms is mediated through local glutamatergic neural systems, specifically through those relying on NMDA receptors. It remains to be determined what factors trigger the increase in orexin activity and whether glutamatergic neurons downstream from the orexinergic neurons are influenced by other factors which may alter their responsiveness to the released orexin.
Publications
- Doane, D.F., Lawson, M.A., Meade, J.R., Kotz, C.M. and Beverly, J.L. 2007. Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus. Am. J. Physiol. 293:R1022-1026.
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Progress 01/01/06 to 12/31/06
Outputs
Two studies were completed using a microdialysis protocol to measure the release of the amino acid neurotransmitters glutamate and GABA in the perifornical region of the lateral hypothalamus in response to exogenous orexin administration. Orexin stimulated feeding for approximately 2 hours after administration. There was a reciprocal response in the release of the two amino acid neurotransmitters: GABA concentrations decreased and glutamate concentrations increased. Dr. Catherine Kotz, at the University of Minnesota and VA system had complimentary data demonstrating that GABA receptor antagonist were effective in reducing the feeding response to orexin. Therefore it was not necessary for us to do the receptor pharmacology experiments for GABA and we consolidated our results with hers (see publication). However, we are conducting the appropriate receptor pharmacology for glutamate receptors to identify whether glutamate is functionally involved with the orexigenic
response to orexin.
Impacts
The results of these studies will improve our understanding of mechanisms in the brain that regulate energy balance and growth. These studies specifically address the neuropeptide Orexin which generates one of the more robust feeding responses. Clarifying the mechanism of this response may allow manipulation to improve efficiency in animal production systems.
Publications
- Thorpe, A.J., Doane, D.F., Sweet, D.C., Beverly, J.L. and Kotz, C.M. 2006. Orexin A in the rostrolateral hypothalamic area induces feeding by modulating GABAergic transmission. Brain Res. 1125(1):60-6, 2006.
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Progress 10/01/05 to 12/31/05
Outputs
Funding for this project began on Oct. 1. Ongoing studies are measuring the release of amino acid neurotransmitters, glutamate and gamma amino butyric acid, in the peri-fornical region (PFA) of the lateral hypothalamus in response to exogenous orexin administered directly into the PFA. Combination microdialysis/microinjection probes are placed directly in the PFA and samples collected before, during, and after orexin administration. Microdialysis samples are analyzed by HPLC using electrochemical detectors. Preliminary results support an increase in glutamate release in the PFA to orexin. Glutamate in the PFA induces eating, consistent with the effect of orexin to stimulate feeding.
Impacts
Strategies to optimize feed intake and energy expenditure to regulate body growth and composition require an understanding of intrinsic neuropeptide systems in the hypothalamus. The results of the proposed studies will complement existing information and contribute to developing new strategies.
Publications
- No publications reported this period
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