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Applying Brainpower to Obesity

Neurons transplanted from healthy donor mice can repair brain circuitry and partially normalize metabolism in obese mice. Neuronal replacement therapy—the idea that donor neurons can repair a brain injured by trauma or neurodegenerative disease—continues to attract considerable interest. Such therapy is fraught with challenges, however, because its success requires that donor neurons differentiate and form synaptic connections with appropriate neurons in the host. Czupryn et al. transplanted immature neurons from the hypothalamus of wild-type donor mice into the hypothalamus of mutant mice that were morbidly obese because of a genetic deficiency of the receptor for leptin, a metabolic hormone that signals in the hypothalamus. The donor neurons differentiated into four distinct neuronal types that formed functional synapses, resulting in restoration of hypothalamic leptin signaling and partial reversal of obesity and metabolic defects in the recipient mice. A. Czupryn, Y.-D. Zhou, X. Chen, D. McNay, M. P. Anderson, J. S. Flier, J. D. Macklis, Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice. Science 334, 1133–1137 (2011). [Abstract] [Full Text]