Exercise, Stress Resilience, and Locus Ceruleus Galanin

 reposted from SfN

Full paper

https://www.jneurosci.org/content/40/39/7464

Exercise, Stress Resilience, and Locus Ceruleus Galanin

Rachel P. Tillage, Genevieve E. Wilson, L. Cameron Liles, Philip V. Holmes, and David Weinshenker

(see pages 7464–7474)

Regular exercise improves mood and cognition, reduces stress, and increases resilience to subsequent stressors. These effects are mediated by multiple signaling pathways that affect synaptic plsticity and neuronal health in several brain areas. Much evidence suggests that exercise promotes stress resilience by increasing production of the neuropeptide galanin in the locus ceruleus, a structure that drives stress responses by releasing norepinephrine throughout the brain. Galanin is expressed in most locus ceruleus neurons, and it can inhibit spontaneous spiking in noradrenergic neurons. Notably, chronic exercise increases galanin levels in the locus ceruleus of rats, and intracerebroventricular infusion of a galanin antagonist blocks the ability of exercise to increase stress resilience. Moreover, intracerebroventricular infusion of galanin increases stress resilience in rats. Because intracerebroventricular treatments can affect galanin signaling in many brain areas, including hypothalamic nuclei involved in stress responses, Tillage et al. examined the effects of overexpressing galanin selectively in noradrenergic neurons in mice.

The authors first confirmed that 3 week access to a running wheel increased exercise, galanin expression, and stress resilience in mice. Indeed, mice ran 10–16 km/d by the third week of wheel access, and galanin expression in the locus ceruleus of these mice was higher than in sedentary controls. Notably, locus ceruleus galanin levels were correlated with the amount of running and with levels of anxiety-like behavior after footshock stress. In particular, whereas stress caused sedentary mice to spend less time in the open arms of an elevated zero maze the next day, it had no effect on mice that had exercised. Importantly, overexpressing galanin in noradrenergic neurons replicated the effects of exercise—preventing stress-induced increases in anxiety-like behavior in the elevated zero maze—but had no effect on baseline behavior or on acute responses to footshock. Finally, optogenetic activation of the locus ceruleus replicated the effects of footshock stress, and overexpressing galanin in the locus ceruleus blocked this effect.

These data strengthen the hypothesis that increases in galanin expression in the locus ceruleus mediate the effect of exercise on stress resilience. Whether this effect stems from suppression of noradrenergic neuronal activity, effects on locus ceruleus target regions, or both should be examined in future studies.

Footnotes

• This Week in The Journal was written by Teresa Esch, Ph.D.