Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed.
Collaborators from Harvard University, Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain.
Supersized. Experiments with mice suggest that transplanted neurons (green, inset) can help repair a genetic defect that causes obesity.
Credit: Oak Ridge National Laboratories (mouse); C. Zhou et al., Science (neuron)
Repair at the cellular-level of the hypothalamus — a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression — indicates the possibility of new therapeutic approaches to even higher-level conditions such as spinal cord injury, autism, epilepsy, ALS (Lou Gehrig’s disease), Parkinson’s disease, and Huntington’s disease.
The researchers call their findings a proof of concept for the broader idea that new neurons can integrate specifically to modify complex circuits that are defective in a mammalian brain.
The researchers are interested in further investigating controlled neurogenesis — directing growth of new neurons in the brain from within — the subject of much of Macklis’ research as well as Flier’s 2005 paper, and a potential route to new therapies.
“The next step for us is to ask parallel questions of other parts of the brain and spinal cord, those involved in ALS and with spinal cord injuries,” Macklis said. “In these cases, can we rebuild circuitry in the mammalian brain? I suspect that we can.”