According to a new research published online in the journal Nature Communications, bone marrow cells that produce brain-derived neurotrophic factor, known to affect regulation of food intake, travel to part of the hypothalamus in the brain where they ‘fine-tune’ appetite.
“We knew that blood cells produced brain-derived neurotrophic factor (BDNF),” said study co-author Prof Lawrence Chan from Baylor College of Medicine’s Diabetes Research Center. “The factor is produced in the brain and in nerve cells as well. We didn’t know why it was produced in blood cells.”
Prof Chan and colleagues looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain’s hypothalamus called the paraventricular nucleus.
“We knew that in embryonic development, some blood cells do go to the brain and become microglial cells,” Prof Chan said. “This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells.”
However, these bone marrow cells produce a bone marrow-specific variant of BDNF, one that is different from that produced by the regular microglial cells already in the hypothalamus. “Only a few of these blood-derived cells actually reach the hypothalamus,” Prof Chan said.
“It’s not very impressive if you look casually under the microscope,” he said. However, a careful scrutiny showed that the branching nature of these cells allow them to come into contact with a whole host of brain cells. “Their effects are amplified.”
“Mice that are born lacking the ability to produce blood cells that make BDNF overeat, become obese and develop insulin resistance. A bone marrow transplant that restores the gene for making the cells that produce BDNF can normalize appetite. However, a transplant of bone marrow that does not contain this gene does not reverse overeating, obesity or insulin resistance.”
“When normal bone marrow cells that produce BDNF are injected into the third ventricle of mice that lack BDNF, they no longer have the urge to overeat. All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity,” Prof Chan said.
The scientists hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion’s share of the work.
“Bone marrow cells are so accessible. If these cells play a regulatory role, we could draw some blood, modify something in it or add something that binds to blood cells and give it back. We may even be able to deliver medication that goes to the brain, crossing the blood-brain barrier. Even a few of these cells can have an effect because their geometry means that they have contact with many different neurons or nerve cells,” Prof Chan concluded.
Bibliographic information: Hiroshi Urabe et al. 2013. Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus. Nature Communications 4, article number: 1526; doi: 10.1038/ncomms2536