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.
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.
