Pre-gestational stress impacts excitability of hippocampal cells in vitro and is associated with neurobehavioral alterations during adulthood

Abstract

Chronic stress during pregnancy or even prior to gestation can negatively affect offspring´s neurobehavioural development. Several studies have shown, that offspring who had experienced excessive stress during gestation had higher rates of cognitive and mood disorders later during adolescence or in adulthood. Hippocampal neurons play a crucial role in the regulation of behavior, mainly in anxiety-related behaviors and spatial learning and memory. Recently, it has been shown, that excessive stress even prior to gestation could interfere with sensitive developmental processes in the brain and may affect hippocampal functioning with severe neurobehavioural consequences in later life. The aim of this work was to investigate the effects of pre-gestational stress of the rat dams on the hippocampal excitability of the pups right after the birth. Neurobehavioural consequences of pre-gestational stress were analyzed during adolescence (35–40 postnatal days) and in early adulthood (75–80 postnatal days). We have shown that even pre-gestational chronic maternal stress increased resting membrane potential, suppressed depolarization-activated action potential firing, and increased spontaneous activity of hippocampal cells from newborn offspring. Altered function of hippocampus was reflected at the behavioural level. Adolescent male offspring of dams exposed stress prior to conception showed hyperactivity-like behaviour in a new stressful environment and increased anxiety-like behaviour during adulthood compared to adult males from non-stress group. Together, this work suggests, that chronic stress even prior to gestation can interfere with functional brain development of the offspring and can cause long-term behavioural changes at the level of neurobehavioural adaptations.