# 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 differences in blood pressure and inflammation in adulthood, offering insights into how childhood poverty may lead to hypertension in humans.

## Contribution

This study reveals sex-specific physiological and inflammatory mechanisms linking early life resource deprivation to adult hypertension in a rodent model.

## Key findings

- LBN males had elevated blood pressure and increased sympathetic nerve activity compared to controls.
- LBN females showed no changes in blood pressure but had increased parasympathetic nerve activity.
- Males exposed to LBN had reduced brain and kidney pro-inflammatory cytokines, 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 life, by using the limited bedding and nesting (LBN) rodent 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), or 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 changes in BP, autonomic activity, and inflammatory factors in the brain and kidney of rats that were exposed to ELS. To induce ELS, we used the limited bedding and nesting (LBN) model. This is a low resource model that reduces bedding and nesting material, during weaning, to create chronic stress for the dam and pups. The LBN model mimics childhood poverty, which is a state of resource deprivation. Poverty is an 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 activity, and/or organ-specific immunotherapies to assist in lowering BP, mitigating organ damage, and lowering the risk of developing cardiovascular, cerebral, and renal diseases in adults who experienced ACEs, such as poverty.

Childhood poverty is a major public health concern that increases the risk of hypertension later in life, with sex differences.The LBN model induces chronic stress by resource deprivation in early life. This rodent model severely limits the bedding and nesting material during weaning to elucidate the sexually dimorphic mechanisms connecting childhood poverty to hypertension.LBN exposure increases BP in males, but not females, possibly due to an increase in sympathetic activity. Furthermore, the reduction in localized pro-inflammatory cytokines in LBN males may be a compensatory mechanism to lower BP and/or prevent tissue damage.Females exposed to the LBN condition may be protected from hypertension and changes in brain and kidney inflammation due to an increase in parasympathetic activity.This study helps uncover potential therapeutic targets and bring awareness to the sex differences involved in hypertension during adulthood, initiated by childhood poverty.

Childhood poverty is a major public health concern that increases the risk of hypertension later in life, with sex differences.

The LBN model induces chronic stress by resource deprivation in early life. This rodent model severely limits the bedding and nesting material during weaning to elucidate the sexually dimorphic mechanisms connecting childhood poverty to hypertension.

LBN exposure increases BP in males, but not females, possibly due to an increase in sympathetic activity. Furthermore, the reduction in localized pro-inflammatory cytokines in LBN males may be a compensatory mechanism to lower BP and/or prevent tissue damage.

Females exposed to the LBN condition may be protected from hypertension and changes in brain and kidney inflammation due to an increase in parasympathetic activity.

This study helps uncover potential therapeutic targets and bring awareness to the sex differences involved in hypertension during adulthood, initiated by childhood poverty.