In the study, the researchers also took tissue samples from some mice after they had euthanized them and found increased activity of genes that produce the proteins in the brain responsible for the stress response. “It’s interesting to note that these effects are present after a brief two-week exposure 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 and was not involved in this study . What Faraco would like to see, however, is data on how overactivation of these key genes is related to the mice’s behavioral response.
Bailey is working on it. Over the next few years, he plans to work with neuroscientists to observe and record how increased salt intake and stress levels translate into aggression or fear-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 closed parts of a maze rather than exploring the open parts where they are more exposed.
Lee Gilman, an assistant professor of behavioral neuroscience, is already conducting these types of experiments in her lab at Kent State University in Ohio, studying how salt intake affects a phenomenon known as contextual fear generalization. This occurs when conditioned fear responses generated in response to experienced threats are stored and expanded to safe stimuli. It is considered a characteristic symptom of anxiety-related disorders. “It’s directly related to fear processes in the brain,” says Gilman.
Anxious mice freeze when exposed to the same context in which something threatening happened. But when conditioned mice go beyond that and freeze in a novel environment they’ve never been in before, “they generalize their fear,” says Gilman. In their study, which is in preprint, male and female mice were conditioned in a chamber with a patterned background, an ethanol-based scent, and a light, and received mild electric shocks on a stainless steel mesh floor.
Four weeks after conditioning, Gilman found that a high-salt diet increased the overall fear response in women, while the same diet reduced fear expression in men, initially surprising the neuroscientist. But in previous behavioral studies of salt intake, most researchers had only experimented with male mice, which would explain these sex differences that are only now emerging.
Although these two studies improve our understanding of the effects of high-salt diets on the brain, Faraco cautions that we must be cautious when extrapolating the findings 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 brief exposure in animal models compared to lifetime exposure in humans, and the known underestimation of human salt consumption.”
Behavioral science 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 mouse behavior over longer periods of time. And while their findings can’t be extrapolated directly to humans, they hope people will become a little more conscious of their salt consumption, both in general and during times of plenty like Christmas. Currently, most consumers pay attention to the calorie and sugar content when they are served a feast at a communal table—”the salt aspect goes very under the radar in people’s consciousness,” says Gilman. That could all change once we figure out how it affects our mood and emotions.