A new neural brain-to-bone pathway that controls the development of bone – which
could help develop future treatments for osteoporosis and neural disorders – has
been discovered by Hebrew University researchers.
The neuronal pathway –
part of the autonomic nervous system – reaches the bones and is involved in
controlling bone density during adolescence, which in turn determines the
skeletal resistance to fracture throughout one’s entire life. Osteoporosis
involves the thinning of the bones, which can result in disability and even
The research was published this week in the American journal PNAS
– Proceedings of the National Academy of Sciences.
included scientists from HU’s bone laboratory, headed by Prof. Itai Bab,
in collaboration with Prof. Raz Yirmiya, head of the laboratory for brain and
behavioral research, along research students Alon Bajayo and Vardit Kram and
master’s degree students Arik Bar and Marilyn Bachar. Additional collaborators
were Dr. Adam Denes of the University of Manchester and Prof. Alberta Zallone
from the University of Bari in Italy.
The brain monitors and regulates
the physiological functioning of the internal organs through the autonomic nerve
systems, which is divided into two subsystems called “sympathetic” and
Each of these subsystems has its own distinct neural
pathways. In general, the sympathetic nervous system is best known for mediating
the neuronal and hormonal responses to stress. The sympathetic pathway usually
functions to maintain the body’s systems when people sleep.
studies by the HU researchers and others showed that the sympathetic nervous
system reaches the skeleton and slows down bone development.
now, there was no information on skeletal parasympathetic activity
To show that there are indeed parasympathetic responses in the
skeleton, the researchers injected a weakened rabies virus – which uniquely
migrates from the injection site in the periphery of the body along nerve fibers
towards the brain – into the thigh bones of mice. Following the shot into the
thigh bone, the virus was found in the brain in regions known to be specific to
the parasympathetic subsystem.
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.
“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,” Yirmiya said.
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
“The new findings ... highlight for the first time an important
physiological role for the connection between interleukin-1 in the brain and the
autonomic nervous system,” he said.