Journal
SCIENCE
Volume 334, Issue 6059, Pages 1133-1137Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1209870
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Funding
- NIH [NS41590]
- Jane and Lee Seidman Fund for Central Nervous System Research
- Emily and Robert Pearlstein Fund for Nervous System Repair
- National Institute of Neurological Disorders and Stroke (NINDS) [NS057444, NS054674, NS070295]
- Ministerstwa Nauki i Szkolnictwa Wyzszego [N303 298437]
- Foundation for Polish Science
- [DKR37-28082]
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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.
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