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

TL;DR

Rats exposed to a low-resource environment early in life show sex-specific changes in blood pressure and inflammation in adulthood, offering insights into how childhood poverty may affect adult health differently in males and females.

Contribution

This study reveals sex-specific physiological and inflammatory mechanisms linking early life poverty to adult hypertension.

Findings

LBN males had elevated blood pressure and increased sympathetic nerve activity compared to controls.

LBN females showed balanced increases in both sympathetic and parasympathetic nerve activity without changes in blood pressure.

LBN males had reduced pro-inflammatory cytokines in the brain, possibly as a compensatory mechanism.

Abstract

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.

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).

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-α, were decreased in the brains of LBN vs. CON males, with no alterations in females.

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-α 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.

People who experience early life stress (ELS), also known as adverse childhood experiences (ACEs), have an increased risk of developing high blood pressure (BP), cardiovascular, cerebral, and renal diseases as adults with sex differences. To explore these sex differences, we examined the BP, changes in autonomic nervous system activity, and inflammatory factors in the brain and kidney of rodents that were exposed to ELS. The ELS rodent model used in this study is the limited bedding and nesting (LBN) model. The LBN model is a chronic stress and low resource model in which the dam (mother) and pups (offspring) experience a lack of access to bedding material for nursing during the weening period. This ELS model mimics childhood poverty, which is a state of resource deprivation and ACE that affects ~ 333 million children worldwide . In this study, we found that ELS induced high BP, increased sympathetic nerve activity (SNA), and decreased pro-inflammatory cytokines in the brain and kidneys of LBN males. However, LBN females displayed a simultaneous increase in SNA and parasympathetic nerve activity (PNA), with no changes in brain and kidney pro-inflammatory cytokines and BP. In summary, these sex differences provide context to the development of high BP caused by resource deprivation during early life. Scientists and medical providers should consider sex, alterations in autonomic nervous system, and/or organ-specific immunotherapies to assist in lowering BP, organ damage, and the risk of developing cardiovascular, cerebral, and renal diseases in adults who experienced ACEs, such as poverty.

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