Neuron transplantation against obesity and diabetes
Neurons transplanted into the hypothalamus restored the sensitivity of the mice to leptin
LifeSciencesToday based on the materials of the Nencki Institute of Experimental Biology (Transplanted cells repair the brain in obese mice) and ScienceNOW (Transplanted Neurons Curb Obesity).
Without neurons that respond to the level of leptin in the blood, the brain cannot control the feeling of hunger and satiety. This type of genetic defect leads to severe obesity in both humans and animals. Scientists from Harvard University (HU), Massachusetts General Hospital (MGH) and the Institute of Experimental Biology named after The Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw demonstrated in experiments on mice that it is possible to restore brain function by transplanting a small number of new neurons into the damaged area of the brain.
"The brilliant effect of brain recovery, which we managed to achieve, is expressed in a significant reduction in the weight of genetically defective obese mice and further pronounced mitigation of side symptoms accompanying diabetes," comments Dr. Artur Czupryn (Artur Czupryn Institute) on the results of the work. Nensky), the first author of an article published in the journal Science (Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice).
Mice that received transplanted cells a few days after birth grew significantly fuller than normal, but did not have pathological obesity. Rodents with transplanted cells weighed on average about 40-45 grams. For comparison, ordinary mice weigh 25 grams, while mutant mice weigh from 55 to 60. In addition, mice with transplanted neurons did not develop diabetes.
Scientists and doctors have been trying for several years to restore damaged areas of the brain through stem cell transplantation. Such interventions are risky: transplanted cells often develop uncontrollably, often leading to cancer.
The aim of the study conducted over the past five years at HU, MGH and the Institute of According to Nensky, it was proved that by transplanting a small number of cells, it is possible to restore missing neural circuits and lost brain functions. In these experiments, genetically modified mice with a deficiency of leptin receptors were used. Leptin is a protein released into the blood by adipose tissue cells during meals. Reaching the hypothalamus, it interacts with certain neurons, and its presence or low level causes a feeling of satiety or hunger, respectively. Mice with a deficiency of leptin receptors do not know the feeling of satiety. They weigh twice as much as healthy animals and suffer from severe diabetes.
Scientists focused their attention on the transplantation of immature neurons (neuroblasts) and progenitor cells - specific stem cells with an already determined direction of development. Cells isolated from small areas of the developing brain of healthy mouse embryos were used for transplantation. Thus, the probability that the cells transplanted into the recipient's brain would transform into neurons and glial cells increased.
As a rule, millions of cells are transplanted. However, in this project, scientists injected a suspension of only a few thousand progenitors and neuroblasts into the hypothalamus of mice. About 300 nanoliters of cell suspension were injected into the hypothalamus by a minimally invasive method – a thin micropipette with a diameter only several times larger than the size of a single cell.
"The suspension is injected into a strictly defined area of the hypothalamus of mice with a length of about 200-400 micrometers. We managed to find it thanks to the unique high-frequency ultrasound microscopic accompaniment available at Harvard University. This made it possible to perform complex non–invasive microtransplantations with unprecedented accuracy, since we could obtain high-resolution images of both brain structures and the inserted micropipette," explains Dr. Chuprin.
All the transplanted cells were labeled with a fluorescent protein, which allowed them to be tracked in the recipients' brains. Observations carried out 20 weeks or more after the procedure showed that almost half of the transplanted cells transformed into neurons with typical morphology, synthesizing proteins characteristic of normal nerve cells. Sophisticated research methods made it possible to demonstrate that the entire spectrum of missing neuron types was restored in the center of control over hunger and satiety. Moreover, the new neurons had already formed synapses and interacted with other neurons in the brain, as well as properly reacted to changes in leptin, glucose and insulin levels.
"To date, many attempts to transplant cells into the brain have been described in the literature. We have shown that a small transplant of neuroblasts and progenitors is really able to restore damaged areas of the brain and affect the entire body. We have shown that it is possible to transplant new neurons that function properly, integrate well into the recipient's nervous tissue and restore lost brain functions. In addition, this method is minimally invasive and safe, as it does not lead to the formation of tumors," sums up Dr. Chuprin.
The results achieved by a group from Harvard University and the Institute. Nensky, determine a promising direction of research that can lead to the development of new methods of restorative therapy. Such methods can, for example, help to eliminate the consequences of a stroke or improve the effectiveness of treatment of Parkinson's disease associated with dysfunction of a certain area of the brain. However, scientists emphasize, it will take many years of experiments, research and tests before therapy based on their ideas will come to clinics and hospitals.
Dr. Arthur Chuprin worked for several years at the Massachusetts General Hospital and Harvard Medical School, and now cooperates with the Institute. Nenskiy. The research groups of Jeffrey Macklis (Jeffrey Macklis), Jeffrey Flier (Jeffrey Flier) and Matthew Anderson (Matthew Anderson) from Harvard Medical School (Harvard Medical School), Massachusetts General Hospital, Harvard Stem Cell Institute (Harvard Stem Cell Institute), Harvard University and Deaconess Beth Israel Medical Center participated in this project (Beth Israel Deaconess Medical Center).
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05.12.2011