title: Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice.
abstract: Evolutionarily old and conserved homeostatic systems in the brain, including the hypothalamus, are organized into nuclear structures of heterogeneous and diverse neuron populations. To investigate whether such circuits can be functionally reconstituted by synaptic integration of similarly diverse populations of neurons, we generated physically chimeric hypothalami by microtransplanting small numbers of embryonic enhanced green fluorescent protein-expressing, leptin-responsive hypothalamic cells into hypothalami of postnatal leptin receptor-deficient (db/db) mice that develop morbid obesity. Donor neurons differentiated and integrated as four distinct hypothalamic neuron subtypes, formed functional excitatory and inhibitory synapses, partially restored leptin responsiveness, and ameliorated hyperglycemia and obesity in db/db mice. These experiments serve as a proof of concept that transplanted neurons can functionally reconstitute complex neuronal circuitry in the mammalian brain.
authors: Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors: Artur
authors: A
authors: Czupryn
authors: Yu-Dong
authors: YD
authors: Zhou
authors: Xi
authors: X
authors: Chen
authors: David
authors: D
authors: McNay
authors: Matthew P
authors: MP
authors: Anderson
authors: Jeffrey S
authors: JS
authors: Flier
authors: Jeffrey D
authors: JD
authors: Macklis
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D048430:Cell Shape; D055724:Electrophysiological Phenomena; D019706:Excitatory Postsynaptic Potentials; D005947:Glucose / Q000008:administration & dosage; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008820:Mice, Obese; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D054411:Receptors, Leptin / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin; D005947:Glucose