New neurons in an old brain
The central nervous system (CNS) contains a diverse set of neuronal subtypes, which together form the complex circuitry that regulates virtually every life function. To maintain normal body function, several systems in mammals require the simultaneous operation of a variety of neuronal subtypes, each sending different endocrine and paracrine messages to the brain. One such system is that of leptin signaling in the hypothalamus. Leptin signaling regulates energy balance, glucose levels, food intake, and body weight. In recent work, Jeffrey Macklis, MD, Leader of HSCI's Nervous System Diseases Program, introduced functional neurons into the hypothalami of mice with faulty leptin signaling pathways. Through a series of controlled experiments, Macklis and his team showed that the donor neurons successfully integrated into the CNS and restored leptin signaling, with the further benefit of ameliorating the obesity and diabetes that had resulted from the damaged state. This work shows that cell therapy can repair a neuronal circuit controlling a complex system and address the resultant diseases.
Czupryn, A.; Zhou, Y.D.; Chen, X.; McNay, D.; Anderson, M.; Flier, J.; Macklis, J. (2011) Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice. Science 334, 1133-1137.