Abstract
•Defects in maternal care behavior persist into the F2 generation.•F2 show depressed maternal care and increased restlessness throughout lactation.•F2 show immune system and hypothalamic pituitary adrenal axis alterations.•Support that the effects of stress can accumulate across multiple generations.
Early adversity such as depressed maternal care can have long-term physiological and behavioral effects on offspring and future generations. Exposure to chronic social stress (CSS), an ethologically model of postpartum depression and anxiety, during lactation impairs maternal care and exerts similar effects on the F1 dam offspring of the stressed F0 dams. These changes associate with increased corticosterone and neuroendocrine alterations. CSS F2 offspring further display decreased social behavior as juveniles and adults and decreased basal levels of corticosterone. This current study investigates the intergenerational inheritance of alterations in maternal behavior in F2 CSS dams together with neuroendocrine and immune markers to explore whether aspects of maternal behavior are intergenerationally inherited through immune and neuroendocrine mechanisms. We find that defects in maternal care behavior persist into the F2 generation with F2 dams exhibiting a pervasively depressed maternal care and increased restlessness throughout lactation. This occurs together with reduced basal cortisol (in contrast to an increase in F1 dams), a lack of changes in neuroendocrine gene expression, and reduced serum ICAM-1 (intercellular adhesion molecule-1) levels - a marker for inflammation and blood–brain barrier integrity. The data support the hypothesis that the effects of chronic social stress can accumulate across multiple generations to depress maternal care, increase restlessness and alter basal functioning of the immune system and hypothalamic pituitary adrenal axis.