Voluntary eating of saltier food by mice and acute stress each abrogate reductions in a neuroinflammatory marker across sexes

Abstract

Both consuming excess salt (NaCl) and experiencing environmental stress can elevate neuroinflammation and enhance risk for non-communicable diseases. Most rodent studies investigating these topics use only males, and assess salt or stress separately. Here, we used adult female and male mice to investigate how the combination of access to food high in salt (4% NaCl, w/w) and experiencing an acute stressor interact to affect levels of a proxy measure for neuroinflammation (Iba1). We hypothesized eating salty food and experiencing stress would each individually augment neuroinflammation, and their combination would be additive. Further, we anticipated salty food consumption would increase active stress coping behaviors, and that all of these effects would be enhanced in female mice. Over 4 or 8 weeks, we further evaluated how mice responded to choice access to low (0.4%) and high salt food simultaneously. Our hypothesis that mice across sexes would eventually prefer high over low salt food was supported, while our expectations regarding neuroinflammation and stress did not consistently align with our findings. Instead, we found modest changes in passive coping behaviors driven by our choice condition, unanticipated reductions in sham stress neuroinflammation by high salt in brain region- and biological sex-specific patterns after 4 weeks, and distinct sex- and salt-selective increases in swim stress neuroinflammation after 8 weeks. Though some of our results were unexpected, they include multiple novel and translationally relevant outcomes. Mice willingly choose to eat saltier food over time, akin to people, and this could sex-specifically decrease (females) or augment (males) passive coping stress strategies while eliciting distinctive stress- and brain region-dependent neuroinflammatory patterns over time. Future studies implementing more complex behavior tests and stress manipulations will advance identification of the hidden ways through which salty food and stressful experiences interact to affect risk for non-communicable diseases.