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March 2, 2026Neurochemical Research1 citationsOpen Access

Prenatal Stress Induces Changes in Behavior, HPA Axis, Inflammation, and Oxidative Stress in Adult Rats Offspring

JAJorge M. Aguiar‐GeraldoJPJefté Peper-NascimentoJCJosé H. Cararo

Key Points

  • To investigate the effects of prenatal stress on behavior and physiological changes in offspring resulting from lithium treatment.
  • Pregnant Wistar rats exposed to chronic unpredictable stress from gestation day 14 until birth.
  • Offspring treated with lithium or saline for seven days on postnatal day 60.
  • Behavior assessed using open field test to evaluate movement and activity levels.
  • Brain dissection performed on dams and offspring to analyze biochemical markers in specific regions.
  • Pro-inflammatory cytokines, oxidative stress, and HPA axis parameters evaluated in serum and brain tissues.
  • Female offspring from stressed dams exhibited hyperactivity in behavioral tests.
  • Increased levels of pro-inflammatory cytokines and oxidative damage markers observed in offspring's brain and serum.
  • Elevated HPA axis hormone levels noted in offspring after prenatal stress exposure.
  • Lithium treatment reduced some biochemical alterations caused by prenatal stress.

Abstract

Prenatal stress is related to the development of psychiatric disorders involving inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the aim of the present study was to evaluate the effects of prenatal stress on behavior, inflammation, oxidative stress, and the HPA-axis in the dams and their offspring treated with lithium. Thirteen pregnant Wistar rats were exposed to a prenatal chronic unpredictable stress protocol from the 14th day of gestation until birth. At the 60th postnatal day (PND), a treatment protocol was carried out in the offspring with lithium (intraperitoneally - 47.5 mg/kg) or saline for seven days (twice a day). The behavior was assessed in the open field test to evaluate free movements. The dams (21 PND) and offspring (after open field) were euthanized, their brains were dissected in frontal cortex, hippocampus, and striatum, and the serum was collected. In the brain and/or serum, the levels of oxidative stress, inflammation, and HPA axis parameters were evaluated. Female offspring from stressed dams showed hyperactivity. Besides behavior alterations, offspring brain and serum showed an increase in pro-inflammatory cytokines, oxidative damage markers, and HPA axis hormones levels. Lithium administration only reduced the biochemical alterations. The prenatal stress protocol induced long-lasting behavior, inflammatory, oxidative stress, and HPA-axis alterations in the offspring which could underlie the development of psychiatric disorders.

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Cite This Study

Aguiar‐Geraldo et al. (2026) studied this question.

synapsesocial.com/papers/69a52e64f1e85e5c73bf212chttps://doi.org/10.1007/s11064-026-04672-3
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