How the different stressors—the salt in the mice’s body and the stressful Plexiglas environment—affect each other and compound is particularly interesting, Bailey continues, because humans are also often exposed to multiple stressors at once. So it’s possible that something similar could be happening in our own bodies. Just think of the last-minute gifting spree or heated debates at the dinner table at Christmas with annoying relatives, which send people’s blood pressure soaring—and then add to this the overindulgence in salty food over the festive season. “I think that for some people, the diet that we’re eating is going to make us deal with it less well than we would otherwise,” says Bailey.
In the study, the researchers also took tissue samples from some mice after euthanizing them and found increased activity of genes that produce the proteins in the brain responsible for the stress response. “It is interesting to notice that these effects are present after a brief exposure of two weeks to a high-salt diet,” says Giuseppe Faraco, an assistant professor of neuroscience at Weill Cornell Medicine, who studies the link between salt and cognitive impairment but wasn’t involved in this study. What Faraco would have liked to have seen, however, is data on how the overactivation of these key genes relates to the behavioral response of the mice.
Bailey is working on that. Over the next few years, he plans to collaborate with neuroscientists to observe and record how increased salt intake and stress levels manifest in aggression or anxiety-like behavior when mice are placed in specially designed mazes. For example, anxious mice tend to seek safety behind opaque walls and spend more time in enclosed parts of a maze rather than exploring the open parts where they are more exposed.
Lee Gilman, an assistant professor of behavioral neuroscience, already conducts these kinds of experiments in their lab at Kent State University in Ohio, examining how salt intake affects a phenomenon known as contextual fear generalization. This occurs when conditioned fear responses, generated in response to threats that have been experienced, become memorized and extended to safe stimuli. It’s considered a hallmark symptom for anxiety-related disorders. “It directly relates to anxiety processes in the brain,” says Gilman.
Fearful mice will freeze when exposed to the same context in which something threatening took place. But when conditioned mice go beyond this and freeze in a novel environment where they have never been before, “they’re generalizing their fear,” Gilman says. In their study, which is in preprint, male and female mice were conditioned in a chamber containing a patterned background, an ethanol-based scent, and a light, receiving mild electric shocks on a floor of stainless-steel grids.