TrkB Neurons of the Paraventricular Hypothalamus Suppress Feeding through Projections to the Parabrachial Nucleus
Obesity is the result of failed energy homeostasis, and is characterized by the progressive accumulation of body weight, with the majority of weight gain due to increased fat mass. The regulation of body weight through energy homeostasis is carried out primarily within the central nervous system. The brain responds to an excess or deficit in caloric availability, and corrects these imbalances by adjusting physiological processes that utilize calories and by influencing cognitive processes such as motivations, decision making, and behavior. However, the biological substrates that perform these corrective actions are susceptible to disruptions from genetic and environmental factors that can reduce their effectiveness. Within the brain, the paraventricular nucleus of the hypothalamus (PVH) is a region highly involved in the integration of energy signals and the coordination of corrective outputs. Here I show that tropomyosin receptor kinase B (TrkB), the receptor for brain-derived neurotrophic factor, is expressed by neurons of the PVH (PVH^TrkB neurons). I also show that TrkB receptors within this nucleus are critical for the suppression of food intake. Using the Cre-Lox system, I demonstrate that the specific post-developmental deletion of TrkB from the PVH produces severe hyperphagic obesity, but not reduced energy expenditure. Moreover, I show that this effect is mediated by the specific population of PVH^TrkB neurons that project to the parabrachial nucleus (PBN) by selectively deleting TrkB only from this population, which recapitulated the hyperphagic obesity phenotype produced by whole PVH TrkB deletion.
Showing items related by title, author, creator and subject.
MMP-1 Overexpression Selectively Alters Inhibition in D1 Spiny Projection Neurons in the Nucleus Accumbens and Disrupts Amphetamine Induced Locomotion Al-Muhtasib, Nour (Georgetown University, 2018)Protease activated receptor-1 (PAR-1) and its ligand, matrix metalloproteinase-1 (MMP-1), are altered in several neurodegenerative diseases. PAR-1 and MMP-1 signaling impact neuronal excitation and inhibition in various ...