Maternal Low Sodium Diet Impairs Hippocampal Neurogenesis and Cognition in Adult Mouse Offspring

Sodium (Na) homeostasis is critical for organ and cell function. While low maternal Na intake during gestation is associated with low offspring survival rates and birth weights, the long-term impact on neurocognitive function is not known. Identifying a relationship between perinatal Na dysregulation and adult behavioral and cognitive outcomes may be important given the prevalence of both dysnatremias and neurocognitive impairment in preterm infants. This study aimed to determine the association between maternal low Na intake (LSI) and hippocampal-dependent behaviors in mice. C57BL/6J dams were fed a standard (0.30%) or low (0.04%) Na diet from postnatal day 0 until postnatal day 21, when pups were weaned onto a standard 2920x (0.15% Na) diet. Behavioral testing and hippocampal analyses were performed in adult mice at 60-80 days of age. Maternal LSI was associated with impaired spatial memory and learning and increased anxiety-like behaviors in offspring in a sex-specific manner. Maternal LSI impaired hippocampal neurogenesis and altered <i>Sox2</i> expression, downstream signaling, and epigenetic regulation. The magnitudes of these effects differed between sexes. Our findings suggest maternal LSI is sufficient to impair hippocampal development and cognitive functions in adult offspring.