Brain circuit linking stress, insomnia and the immune system discovered

A new study, led by neuroscientists from Stanford University, has homed in on the specific brain circuit responsible for stress-induced insomnia. The research suggests this same circuit is responsible for stress-related immune system dysfunction, pointing to a close relationship between stress, insomnia and weakened immunity.

It is well known that psychosocial or environmental stress can lead to immune system abnormalities. Insomnia is also commonly associated with stress. But ... do these two stress-induced conditions share the same neural circuitry?

“This sort of stress-induced insomnia is well known among anybody that’s tried to get to sleep with a looming deadline or something the next day,” says Jeremy Borniger, one of the authors on the new study. “And in the clinical world, it’s been known for a long time that chronically stressed patients typically do worse on a variety of different treatments and across a variety of different diseases.”

Using a transgenic mouse model, the researchers first pinpointed a cluster of neurons in the paraventricular nucleus of hypothalamus responsible for the stress-induced release of cortisol. Activity in this brain area was found in stimulate a nearby cluster of neurons in the lateral hypothalamus. This area in the lateral hypothalamus was seen to elicit a kind of hyperarousal associated with insomnia.

Using optogenetics the researchers could either block this novel neural circuit, causing the mice to sleep comfortably after exposure to a stressful experience, or specifically activate the stress-responsive neurons and watch the animals immediately wake from slumber.

“It seems like it’s a pretty sensitive switch, in that even very weak stimulation of the circuit can drive insomnia,” adds Borniger.

The researchers then looked closely at the effects of stimulating this stress-induced neural pathway on immune system activity. Peripheral immunosuppression was indeed triggered by this same neural pathway. This suggests the effect stress has on both wakefulness and the immune system is, in part, related to this initial, cortisol-releasing, neural pathway.

Borniger says understanding how stress triggers both insomnia and immunosuppression helps researchers look to novel treatments for a number of autoimmune diseases. Interfering with this brain circuit could offer new ways to treat disease. And, of course, new ways to potentially reduce the negative effects of stress on our sleep.

"I'm really interested in how we can manipulate distinct circuits in the brain to control not just the immune system at baseline, but in disease states like inflammatory bowel disease or in cancer or in psoriasis—things that are associated with systemic inflammation,” says Borniger. “Because if we can understand and manipulate the immune system using the natural circuitry in the body rather than using a drug that hits certain targets within the system, I think that would be much more effective in the long run, because it just co-opts the natural circuits in the body."

The new study was published in the journal Science Advances.

Source: Cold Spring Harbor Laboratory