title: TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin.
abstract: Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute to the central nervous system (CNS) control of energy balance. The role of hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined here. Hindbrain ventricular BDNF suppressed body weight through reductions in overall food intake and meal size and by increasing core temperature. To localize the neurons mediating the energy balance effects of hindbrain ventricle-delivered BDNF, ventricle subthreshold doses were delivered directly to medial nucleus tractus solitarius (mNTS). mNTS BDNF administration reduced food intake significantly, and this effect was blocked by preadministration of a highly selective TrkB receptor antagonist {[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and leptin interact with melanocortin signaling to reduce food intake, we also examined whether the intake inhibitory effects of hindbrain leptin involve hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal vagal complex of the hindbrain was increased significantly by hindbrain leptin delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin signaling in the control of energy balance, leptin and ANA-12 were coadministered into the mNTS. Administration of the TrkB receptor antagonist attenuated the intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor activation contributes to the mediation of the anorexigenic effects of hindbrain leptin. Collectively, these results indicate that TrkB-mediated signaling in the mNTS negatively regulates food intake and, in part, the intake inhibitory effects of leptin administered into the NTS.
authors.affiliation: Dept. of Psychology, Univ. of Pennsylvania, 3720 Walnut St., Philadelphia, PA 19104, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Spaeth
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kanoski
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Grill
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D020546:Fourth Ventricle / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D053486:Melanocortins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: C559317:ANA 12 compound; D001381:Azepines; D001549:Benzamides; D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D053486:Melanocortins; D020813:Receptor, trkB