Document Type

Article

Publication Date

5-2026

Identifier

DOI: 10.1152/ajpregu.00304.2025

Abstract

Sodium (Na) homeostasis is critical for organ and cell function. Although 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 Sox2 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.

NEW & NOTEWORTHY An adverse perinatal environment results in increased risk of long-term health morbidity. Pregnancy and lactation are common times for women to alter their diets. Maternal low-sodium diet resulted in impaired offspring spatial memory and learning associated with hippocampal neurogenesis. Adequate maternal sodium intake is essential for neurodevelopment of offspring.

Journal Title

American journal of physiology. Regulatory, integrative and comparative physiology

Volume

330

Issue

5

First Page

463

Last Page

477

MeSH Keywords

Animals; Hippocampus; Neurogenesis; Female; Mice, Inbred C57BL; Cognition; Pregnancy; Male; Prenatal Exposure Delayed Effects; Behavior, Animal; Diet, Sodium-Restricted; Maternal Nutritional Physiological Phenomena; Mice; Anxiety; SOXB1 Transcription Factors; Spatial Memory; Epigenesis, Genetic

PubMed ID

41902531

Keywords

behavior; epigenetics; offspring; programming; sodium

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