Neural Pathway Controlling Skeletal Development
Researchers have discovered a neural pathway in the parasympathetic nervous system that reaches the bones and participates in the control of bone development
This neural pathway, part of the autonomic nervous system, has a key role in controlling bone density during adolescence, which in turn determines the skeletal resistance to fracture throughout one's entire life, say the Hebrew University of Jerusalem researchers.
They emphasize that understanding the mechanisms connecting the brain and the bones could have implications for future therapies improving treatment of osteoporosis and various neural disorders.
The findings of the Hebrew University team are published this week in the American journal PNAS (Proceedings of the National Academy of Sciences).
The autonomic nervous system, by which the brain monitors and regulates the functioning of our internal organs, includes two subsystems, the "sympathetic" and "parasympathetic."
Each of these subsystems has its own, distinct neural pathway. In general, the sympathetic nervous system is perhaps best known for mediating our neural and hormone responses to stress. The parasympathetic pathway generally promotes maintenance of the body at rest.
Previous studies have shown the
sympathetic nervous system reaches the skeleton
and slows down bone development.
But until now, there was no information on skeletal
parasympathetic activity in bone development.
To demonstrate that there are indeed parasympathetic responses in the skeleton, 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.
Previous research by this same group reported how the activity of a protein called interleukin-1 influences bone development. Now they notice that the interleukin-1 influence is very similar to that of the parasympathetic subsystem.
The new research shows that deactivating interleukin-1
activity in the brain of laboratory mice
paralyzes parasympathetic activity in the bone
and slows down skeletal development.
Further, it was discovered that this neural pathway,
which influences interleukin-1 in the brain
as part of the parasympathetic subsystem,
also controls our heart rate.
As influencial on the bone and the heart, the new pathway might have an important function as well on other organs controlled by the autonomic nervous system.
Prof. Yirmiya: "low bone density 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."
Prof. Bab: "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. The new findings, discovered in our Hebrew University laboratories, highlight for the first time an important physiologic 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.
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.
Original article: http://www.eurekalert.org/pub_releases/2012-09/thuo-nnp090312.php