Rats Exposed to a Low Resource Environment in Early Life Display Sex Differences in Blood Pressure, Autonomic Activity, and Brain and Kidney Pro-inflammatory Markers During Adulthood

Smith, J.; Smith, S.; Jones, K.; Castillo, A.; Bolton, J.; Howard, A.; Colon-Perez, L.; Femi-Ogunyemi, F.; Burkes, A.; Cunningham, M. W.

doi:10.1101/2025.09.04.674369

bioRxiv · 10.1101/2025.09.04.674369

Rats Exposed to a Low Resource Environment in Early Life Display Sex Differences in Blood Pressure, Autonomic Activity, and Brain and Kidney Pro-inflammatory Markers During Adulthood

Smith, J.·Smith, S.·Jones, K.·Castillo, A.·Bolton, J.·Howard, A.·Colon-Perez, L.·Femi-Ogunyemi, F.·Burkes, A.·Cunningham, M. W.

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Abstract

Introduction: Poverty, a low resource state, is a common adverse childhood experience (ACE) and early life stress (ELS). People who experienced childhood poverty are at greater risk for developing hypertension during adulthood, with sex differences. To determine the possible mechanisms of these sex differences, we investigated the alterations in blood pressure (BP), autonomic activity, and inflammation in the brain and kidneys of rats exposed to an impoverished environment during the early postnatal period, by using the limited bedding and nesting (LBN) model. Methods: The LBN model mimics childhood poverty by creating a low resource environment on postnatal days 2-9. After weaning, offspring were separated by sex and LBN exposure and were evaluated at 16-18 weeks of age (Adulthood). Results: LBN males displayed an increase in BP compared to the control (CON), whereas LBN females showed no changes. Sympathetic nerve activity (SNA) was increased in LBN males and females compared to the CON, while only parasympathetic nerve activity (PNA) was increased in LBN vs. CON females. Pro-inflammatory cytokines, IL-17 and TNF-, were decreased in the brains of LBN vs. CON males, with no alterations in females. Conclusion: Adult LBN males have elevated BP, due to increased SNA, while LBN females may be protected from increased BP due to a simultaneous increase in SNA and PNA. The reduction in IL-17 and TNF- in LBN males may serve as a compensatory mechanism to lower BP. This study provides insights into sex differences in BP for adults who experienced childhood poverty.

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Smith, J., Smith, S., Jones, K., Castillo, A., Bolton, J., Howard, A., Colon-Perez, L., Femi-Ogunyemi, F., Burkes, A., Cunningham, M. W.. 2025-09-09. Rats Exposed to a Low Resource Environment in Early Life Display Sex Differences in Blood Pressure, Autonomic Activity, and Brain and Kidney Pro-inflammatory Markers During Adulthood. https://doi.org/10.1101/2025.09.04.674369

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