Study finds new neural brain-to-bone pathway controlling skeletal development

September 3, 2012

Researchers at the Hebrew University of Jerusalem have discovered that a neuronal pathway—part of the autonomic nervous system—reaches the bones and participates in the control of bone development.

The newly discovered pathway has a key role in controlling density during adolescence, which in turn determines the skeletal resistance to fracture throughout one's entire life, say the researchers. They emphasize that understanding the mechanisms connecting the and the bones could have implications for possible future therapies to better deal with osteoporosis and various neural disorders. The findings of the Hebrew University team are published this week in the journal PNAS ().

 Participants in the project were researchers from the Hebrew University's Bone Laboratory, headed by Prof. Itai Bab, in collaboration with Prof. Raz Yirmia, the head of the Laboratory for Brain and Behavioral Research, plus research students Alon Bajayo and Vardit Kram and master's students Arik Bar and Marilyn Bachar. Additional collaborators were Dr. Adam Denes from the University of Manchester, UK, and Prof. Alberta Zallone from the University of Bari, Italy.

The , by which the brain monitors and regulates the physiological functioning of the , includes two subsystems, called "sympathetic" and "parasympathetic." Each of these subsystems has its own, distinct . In general, the is perhaps best known for mediating the neuronal and hormonal responses to stress. The sympathetic pathway, on the other hand, generally works to promote maintenance of the body at rest.

Previous studies by the Hebrew University researchers and others showed that the sympathetic reaches the skeleton and slows down . On the other hand, until now, there was no information on skeletal parasympathetic activity there.

To demonstrate that there are indeed parasympathetic responses in the skeleton, the researchers injected a weakened rabies virus into the thigh bones of mice. The rabies virus has a unique feature—it migrates from its injection site in the periphery along nerve fibers towards the brain. Following injection to the thigh bone, the virus was found in the brain in regions known to be specific for the parasympathetic subsystem.

In the past, these same researchers reported that the activity of a protein called interleukin-1 influences bone development. Now they noticed that this influence is very similar to that of the parasympathetic subsystem. Indeed, the researchers showed that deactivating interleukin-1 activity in the brain of laboratory mice paralyzes parasympathetic activity in the bone and slows down skeletal development. They further found that the newly discovered neuronal pathway, which includes interleukin-1 in the brain and the parasympathetic subsystem, also controls the heart rate.

As in the bone and the heart, the new pathway might have an important function as well in other organs controlled by the autonomic nervous system. Prof. Yirmiya said that "low and osteoporosis often appear together with neuropsychiatric disorders such as depression, Alzheimer's disease and epilepsy, since interleukin-1 in the brain and the parasympathetic system are often damaged in these disorders. Finding the disease mechanisms in these cases has a huge potential for the development of new therapies," he added.

"The connection between the brain and the bone in general and the involvement of the newly discovered pathway in particular is a new area of research about which we still know very little," said Prof. Bab. "The new findings, discovered in our Hebrew University laboratories, highlight for the first time an important physiological role for the connection between interleukin-1 in the brain and the autonomic nervous system.

The research has been conducted as part of a project to study the connection between the activity of interleukin-1 in the brain, the parasympathetic system and the skeleton. It was supported by the German-Israeli Foundation for Scientific Research and Development and by the Israel Science Foundation.

Explore further: 'Mad cow disease' in cattle can spread widely in ANS before detectable in CNS

More information: Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual, PNAS, Sept. 3, 2012.

Related Stories

'Mad cow disease' in cattle can spread widely in ANS before detectable in CNS

July 9, 2012
Bovine spongiform encephalopathy (BSE, or "mad cow disease") is a fatal disease in cattle that causes portions of the brain to turn sponge-like. This transmissible disease is caused by the propagation of a misfolded form ...

Recommended for you

Gene therapy improves immunity in babies with 'bubble boy' disease

December 9, 2017
Early evidence suggests that gene therapy developed at St. Jude Children's Research Hospital will lead to broad protection for infants with the devastating immune disorder X-linked severe combined immunodeficiency disorder. ...

In lab research, scientists slow progression of a fatal form of muscular dystrophy

December 8, 2017
In a paper published in the Nature journal Scientific Reports, Saint Louis University (SLU) researchers report that a new drug reduces fibrosis (scarring) and prevents loss of muscle function in an animal model of Duchenne ...

Double-blind study shows HIV vaccine not effective in viral suppression

December 7, 2017
(Medical Xpress)—A large team of researchers from the U.S. and Canada has conducted a randomized double-blind study of the effectiveness of an HIV vaccine and has found it to be ineffective in suppressing the virus. In ...

Time matters: Does our biological clock keep cancer at bay?

December 7, 2017
Our body has an internal biological or "circadian" clock, which cycles daily and is synchronized with solar time. New research done in mice suggests that it can help suppress cancer. The study, publishing 7 December in the ...

Novel harvesting method rapidly produces superior stem cells for transplantation

December 7, 2017
A new method of harvesting stem cells for bone marrow transplantation - developed by a team of investigators from the Massachusetts General Hospital (MGH) Cancer Center and the Harvard Stem Cell Institute - appears to accomplish ...

Inhibiting TOR boosts regenerative potential of adult tissues

December 7, 2017
Adult stem cells replenish dying cells and regenerate damaged tissues throughout our lifetime. We lose many of those stem cells, along with their regenerative capacity, as we age. Working in flies and mice, researchers at ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.