Dietary Salt Exerts Sex-Specific Effects on Indicators of Neurodegeneration Risk

Much neurodegenerative disease research has focused on treatments or mitigation strategies after symptoms become pervasive. Longitudinal and retrospective studies in humans, and experimental studies in rodents, indicate that environmental stressor exposure and dietary composition each can influence levels of early stage neurodegenerative disease risk indicators (e.g., neuroinflammation, cognitive performance). The interaction of stress and diet upon such early stage risk indicators for neurodegenerative diseases is less explored. Dietary salt (NaCl), a non-caloric food additive implicated in many indicators of neurodegeneration risk, is particularly understudied in conjunction with stress. Indeed, relatively little is known about how dietary salt affects behaviors, particularly across biological sexes. Evidence for sex-specific differences in a marker for neuroinflammation is discussed in mice assigned to low or high salt diets prior to experiencing an acute stressor. Also reviewed are data evaluating how short- and long-term performance of rats in a stressful operant learning task were affected by salt diet and biological sex. While studying rodents is not without limitations, these findings showcase how rigorous control of dietary salt intake in combination with consistent application of single or repeated stressors can reveal nuanced, biological sex-specific outcomes. Implications for biological sex considerations along with stress and salt intake upon neurodegenerative disease risk are discussed, with a focus on early stage risk evaluation, and acknowledgement that replication and additional studies are important.

Learning Objectives:

1. Review indicators of neurodegenerative risk associated with salt intake.

2. Criticize the generalizing of salt behavior findings that have historically excluded biological females.

3. Evaluate the merits and detractions of studying dietary salt + stress interactions in rodents.