Designing a mouse model to study immune responses to socioeconomic-related early life stressors

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Early life stress (ELS) is associated with a range of negative effects on long-term human health. With increased concerns over child abuse during the COVID-19 pandemic, there is a need for a deeper understanding of how ELS affects immune system programming and development. Neglect is a significant source of ELS during childhood and accounts for 80% of reported abuse and over 30% of maltreatment-related deaths in the United States. Malnutrition in children due to neglect results in poor growth (failure to thrive) and increases the risk of poor health outcomes. Literature suggests children from low socioeconomic status families struggling with economic hardship are more likely to experience neglect. Animal models of ELS emulate the nature of childhood neglect through scheduled separation. In the present study, we describe a modified version of the maternal separation with early weaning (MSEW) paradigm to emulate neglect-related ELS in C57BL/6 mice based on daily separation and nutritionally defined diet sources (standard chow vs. high carbohydrate). We compare the combined effect of the described MSEW protocol on peripheral stress hormones and cytokine profiles of select primary lymphoid tissue. Pups were produced via in-house breeding procedures and subjected to our modified MSEW protocol. Euthanasia occurred on postnatal day (PD) 21 for tissue harvest and blood collection via cardiac puncture. Cytokines and serum catecholamine and corticosterone levels were detected using commercially available ELISA. Preliminary data suggests the composition of early life diet affects cytokine production within select lymphoid tissues at PD21. This pilot study sheds light on the impact socioeconomic-related early life stressors, such as neglect and poor diet quality, may have on immune outcomes.

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