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Updated: Jul 1, 2025

Author Spotlight: Exploring Microglial Interactions with Stress-Response Circuitry Using the Limited Bedding and Nesting Model
Published on: July 12, 2024
Early life nutrient restriction affects hypothalamic-pituitary-interrenal axis gene expression in a diet
Alexander M Shephard1, Sarah R Lagon2, Cristina C Ledón-Rettig2
1Department of Biology, Indiana University at Bloomington, Bloomington, IN, USA; Department of Biology, Indiana University at Bloomington, 915 East 3(rd) Street, Myers Hall, Bloomington, IN 47405, USA.
Abstract:
Stressful experiences in early life can alter phenotypic expression later in life. For instance, in vertebrates, early life nutrient restriction can modify later life activity of the hypothalamic-pituitary-adrenal/interrenal axis (the HPI in amphibians), including the up- and downstream regulatory components of glucocorticoid signaling. Early life nutrient restriction can also influence later life behavior and metabolism (e.g., fat accumulation). Yet, less is known about whether nutrient stress-induced carryover effects on HPA/HPI axis regulation can vary across environmental contexts, such as the type of diet on which nutrient restriction occurs. Here, we experimentally address this question using the plains spadefoot toad (Spea bombifrons), whose larvae develop in ephemeral habitats that impose intense competition over access to two qualitatively distinct diet types: detritus and live shrimp prey. Consistent with diet type-specific carryover effects of early life nutrient restriction on later life HPI axis regulation, we found that temporary nutrient restriction at the larval stage reduced juvenile (i.e., post-metamorphic) brain gene expression of an upstream glucocorticoid regulator (corticotropin-releasing hormone) and two downstream regulators (glucocorticoid and mineralocorticoid receptors) only on the shrimp diet. These patterns are consistent with known diet type-specific effects of larval nutrient restriction on juvenile corticosterone and behavior. Additionally, larval nutrient restriction increased juvenile body fat levels. Our study indicates that HPA/HPI axis regulatory responses to nutrient restriction can vary remarkably across diet types. Such diet type-specific regulation of the HPA/HPI axis might provide a basis for developmental or evolutionary decoupling of stress-induced carryover effects.
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