title: NR2B subunit of the NMDA glutamate receptor regulates appetite in the parabrachial nucleus.
abstract: Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing agouti-related protein (AgRP) in adult mice leads to anorexia and starvation within 7 d that is caused by hyperactivity of neurons within the parabrachial nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic plasticity-based behavioral modifications, we hypothesized that modulation of the NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to the anorexia phenotype. We observed by Western blot analyses that ablation of AgRP neurons results in enhanced expression of NR2B along with a modest suppression of NR2A. Interestingly, systemic administration of LiCl in a critical time window before AgRP neuron ablation abolished the anorectic response. LiCl treatment suppressed NR2B levels in the PBN and ameliorated the local Fos induction that is associated with anorexia. This protective role of LiCl on feeding was blunted in vagotomized mice. Chronic infusion of RO25-6981, a selective NR2B inhibitor, into the PBN recapitulated the role of LiCl in maintaining feeding after AgRP neuron ablation. We suggest that the accumulation of NR2B subunits in the PBN contributes to aphagia in response to AgRP neuron ablation and may be involved in other forms of anorexia.
authors: Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Qi
authors: Q
authors: Wu
authors: Ruimao
authors: R
authors: Zheng
authors: Dollada
authors: D
authors: Srisai
authors: G Stanley
authors: GS
authors: McKnight
authors: Richard D
authors: RD
authors: Palmiter
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D054369:Agouti-Related Protein / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003680:Deglutition Disorders / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D004435:Eating / Q000187:drug effects / Q000502:physiology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010636:Phenols; D010880:Piperidines / Q000494:pharmacology; D011149:Pons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D014628:Vagotomy
chemical_list: D000276:Adjuvants, Immunologic; D054369:Agouti-Related Protein; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D018021:Lithium Chloride
keywords: NR2B signaling; feeding behavior; nausea
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