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In a new study, researchers discovered a relationship between a specific bone hormone and brain development and cognition. The research team from Columbia University Medical Center (CUMC) studied the bone-derived hormone, osteocalcin and found that this hormone greatly affects brain functions, such as learning, memory, anxiety and depression. The researchers believe that these findings, even though the study was done on mice models, could help with future research on neurologic disorders.

"The brain is commonly viewed as an organ that influences other organs and parts of the body, but less often as the recipient of signals coming from elsewhere, least of all, the bones," said study leader Gerard Karsenty, MD, PhD, Paul A. Marks Professor of Genetics and Development, professor of medicine, and chair of the Department of Genetics and Development. "In an earlier study, we showed that the brain is a powerful inhibitor of bone mass accrual. This effect was so powerful that it immediately raised the question, 'Does the bone signal back to the brain to limit this negative influence?' 'If so, what signals does it use and how do they work?'"

For this study, the research team genetically altered mice that could not produce osteocalcin. For the first part of the study, the researchers observed brain development and found that the osteocalcin-null mice had abnormally small hippocampi, which is a part in the brain that is responsible for memory. By studying the absence of the osteocalcin, the researchers also found that the bone hormone was capable of crossing the blood-brain barrier. When it did cross over, it bonded to neurons in three main regions of the brain, which were the brainstem, midbrain and hippocampus. The hormone then helped promote the production of neurons and increased the synthesis of neurotransmitters, serotonin, dopamine and catecholamine.

In the latter part of the study, the researchers put the mice through a series of behavioral tests. They observed that the osteocalcin-null mice had more anxiety and depression-related behaviors. They also had impaired learning and memory. The researchers then tried to infuse osteocalcin to the adult osteocalin-null mice and found that anxiety and depression symptoms decreased. However, the mice's learning and memory complications were not positively affected.

The researchers believe that their findings could be applied to cognitive deterioration seen in seniors. The researchers reasoned that as people age, their bone mass and production of this particular bone hormone decrease, which could lead to impaired cognitive functions.

"We're currently looking into this. It is not inconceivable that treatments that boost osteocalcin levels or stimulate osteocalcin receptors could help counter the cognitive effects of aging and aging-related diseases such as Alzheimer's," said Karsenty.

The study was published in Cell.