The physical effects of this are well known. As salt levels rise, so does blood pressure, which can increase the risk of a heart attack or stroke. But scientists think that salt could also have another influence: on behavior. In particular, they’re beginning to unpick how it’s linked to stress. The topic has, until recently, been underexplored, as the impact of salt is a difficult subject to examine in humans. Monitoring people’s salt intake, even under controlled conditions, is hard because of how ubiquitous it is in our food. Plus, since salt can increase blood pressure acutely and over time, knowingly adding salt to the diet of study participants poses an ethical problem. So researchers at the University of Edinburgh have been running experiments with the next best thing: mice. They’re very similar to humans in terms of anatomy, physiology, and genetics—and how both species respond to stress is governed by factors that can include diet, explains Matthew Bailey, a professor of renal physiology at the university. Mice also typically don’t eat a lot of salt, which makes testing its impact on them easier. To investigate the link between salt intake and stress, Bailey and his colleagues fed male mice—some for two weeks, some for up to eight weeks—a high-salt diet, containing a proportion of salt similar to the typical intake of humans. When the researchers then analyzed blood samples from the mice, they found that levels of the stress hormone cortisol were always higher in those on the high-salt diet compared to mice in the control group consuming low levels of salt—both when they were in a resting state and after being restrained in a Plexiglas tube to induce stress. The stress response wasn’t turned on and off by adding salt to the mice’s diet, but amplified, Bailey explains. “It’s like a dimmer switch in a light,” he says. “The stress system was kind of turned on a little bit more.” 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. 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. Four weeks after conditioning, Gilman found that a high-salt diet increased the generalized fear response in females, while the same diet reduced the fear expression in males, which surprised the neuroscientist at first. But in previous behavioral studies on salt intake, most researchers had experimented only with male mice, which would explain these sex differences only now becoming apparent. Although these two studies better our understanding of the effects of a high-salt diet on the brain, Faraco warns that we need to be careful about translating the results to humans. There are differences in how animals and humans absorb, use, and metabolize salt, he says. “Comparisons between rodents and humans must be interpreted with caution, given the uncertainty in estimating minimum salt requirements in mice, the relatively short exposure in animal models compared to lifetime exposure in humans, and the known underestimation of human salt consumption.” Behavioral research is still in its infancy when it comes to salt, but Bailey and Gilman are both working to improve and expand their experiments to track the behavior of mice over longer periods of time. And while their findings cannot be directly extrapolated to humans, they hope that people will be a little more conscious of their salt consumption, both in general and at times of abundance like Christmas. Currently, most consumers pay attention to the calorie and sugar content when being served a feast at a communal table—“the salt aspect goes very much under the radar in people’s awareness,” says Gilman. That could all change if we discover just what impact it has on our mood and how we feel.
