Discovering the surprising effects of the brain’s stress chemical

2019

Challenge

Norepinephrine, a chemical released by certain neurons in the brain, has long been regarded as a stress chemical that triggers anxiety. Research supporting this understanding has been focused on norepinephrine-secreting nerve cells in a region deep inside the brainstem called the locus coeruleus. However, studies have shown that these sorts of nerve cells, called noradrenergic neurons, are present in other areas of the brain. What’s more, research suggests noradrenergic neurons outside the locus coeruleus may not have the same effect on anxiety as their counterparts in that part of the brain.

Advance

IRP researchers led by senior investigator Patricia Jensen, Ph.D., identified noradrenergic neurons outside the locus coeruleus that express a gene called Hoxb1 early in development. When these nerve cells are activated in mice, they mimic the effects of antidepressants by promoting a better coping response to stress and decreasing anxiety-like behavior. These results contrast with the general belief that all noradrenergic neurons promote a stress response, demonstrating the diverse functions these cells have in the brain.

Impact

This study indicates that clinicians and researchers should exercise caution when interpreting how drugs and experiments affect noradrenergic neurons and the influences of norepinephrine in the brain. Recognizing that noradrenergic neurons have diverse functions may help researchers better understand why certain antidepressants that target the entire noradrenergic system have inconsistent results in patients.

Publications

Chen YW, Das M, Oyarzabal EA, Cheng Q, Plummer NW, Smith KG, Jones GK, Malawsky D, Yakel JL, Shih YI, Jensen P. (2019). Genetic identification of a population of noradrenergic neurons implicated in attenuation of stress-related responses. Mol. Psychiatry. May; 24(5):710-725. doi: 10.1038/s41380-018-0245-8.

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