Bone not adrenaline drives fight or flight response.
The fight-or-flight response, also known as the acute stress response (ASR), is a physiological reaction mediated by the sympathetic nervous system which plays a critical role in helping animals react to potentially life-threatening situations. More specifically, the adrenal glands, which sit on top of the kidneys, release a variety of hormones such as adrenaline, norepinephrine, and cortisol which in turn triggers physiological responses. However, as these glucocorticoid hormones require hours to alter physiological responses, there appears to be a gap in theory of an immediate response to danger. Now, researchers at Columbia University shows in bony vertebrates the ASR is not possible without osteocalcin, a hormone produced by bone. The team state that almost immediately after the brain recognizes danger in mice and humans, it instructs the skeleton to flood the bloodstream with osteocalcin, which is needed to turn on the fight or flight response. The opensource study is published in the journal Cell Metabolism.
Previous studies show that the bones which make up the skeleton secrete a protein called osteocalcin which rebuilds the skeleton. Past studies from the group showed this protein acts as a hormone to keep blood sugar levels in check and burn fat. Later, they showed that the hormone is important for maintaining brain function and physical fitness, restoring memory in aged mice and boosting performance during exercise in old mice and people. The findings led the researchers to hypothesize that animals evolved bony skeletons to memorise and escape danger. The current study shows both rodents and humans release a bone-derived hormone called osteocalcin in response to acute stress.
The current study exposes mice to several stressors, including a mild electric shock to the foot and a whiff of fox urine, and then measures the levels of osteocalcin in the animals’ blood. Results show within 2 to 3 minutes of being exposed to a stressor, levels of osteocalcin in the mice quadrupled. Data findings show when participants were asked to speak in front of an audience, osteocalcin levels also spiked.
Results show when osteocalcin levels increased, heart rate, body temperature, and blood glucose levels in the mice also rose as the fight or flight response kicked in. Data findings show in contrast, mice that had been genetically engineered so they were unable to make osteocalcin or its receptor were totally indifferent to the stressor, with ASR induced simply by injecting osteocalcin.
The team surmise their findings suggest osteocalcin, not adrenaline, is the gatekeeper which determines when bodies shift into fight-or-flight mode. For the future, the researchers state their study raises the question of why cortisol rises during the ASR, and now plan to expand their studies to primates to help define the neuronal road map from the brain to the bone in more detailed ways.