Lack of Social Support Raises Stress Vulnerability in Rats with a History of Ancestral Stress

Abstract

Stress is a primary risk factor for psychiatric disorders. However, it is not fully understood why some stressed individuals are more vulnerable to psychiatric disorders than others. Here, we investigated whether multigenerational ancestral stress produces phenotypes that are sensitive to depression-like symptoms in rats. We also examined whether social isolation reveals potentially latent sensitivity to depression-like behaviours. F4 female rats born to a lineage of stressed mothers (F0-F3) received stress in adulthood while housed in pairs or alone. Social isolation during stress induced cognitive and psychomotor retardation only in rats exposed to ancestral stress. Social isolation also hampered the resilience of the hypothalamic-pituitary-adrenal axis to chronic stress and reduced hippocampal volume and brain-derived neurotrophic factor (BDNF) expression. Thus, synergy between social isolation and stress may unmask a latent history of ancestral stress, and raises vulnerability to mental health conditions. The findings support the notion that social support critically promotes stress coping and resilience.

Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes

“…Lack of social support during pregnancy is associated with poor birth outcomes as well as perinatal depression (44,(74)(75)(76)(77). Preclinical (78) and translational studies (79,80) indicate that social isolation hampers effective hypothalamic-pituitary-adrenal-axis regulation, reduces brain-derived neurotrophic factor expression, and amplifies proinflammatory processes identified at the molecular level-each potentially involved in maternal mental and physical health and contributing to offspring outcomes (81). From the perspective of solution-oriented research (82), these findings suggest that social support is a modifiable target for clinical engagement that could benefit women and their future children (83).…”

Infrared Thermography Reveals Sex-Specific Responses to Stress in Mice

“…HPA axis hyperactivity is a characteristic aspect of responses to either transient or repeated stressful experiences in rodents, which is typically accompanied by increased circulating CORT concentration (Markham et al, 2006;Gourley et al, 2013;Browne et al, 2014;Faraji et al, 2014Faraji et al, , 2017. Higher hormonal output in the female stress response particularly during short-term stress (Goel and Bale, 2008;Sterrenburg et al, 2012) not only indicates that their HPA axis function initiates more rapidly than that of males (Iwasaki-Sekino et al, 2009) and remains elevated for longer (Jadavji and Metz, 2008), but also shows that females are endowed with a natural hormonal capacity to regulate stress responses that differs from males (Rhodes et al, 2001;Goldstein et al, 2010).…”

Why and how the early-life environment affects development of coping behaviours

“…The advantage of ancestral stress disappeared when rats experienced another stressor in adulthood, suggesting multiple stressors may limit behavioural flexibility rather than improve it (Faraji et al 2017 ), even in a system where ancestral stress leads to adaptive developmental adjustments. In similar studies, social isolation during later-life stress caused cognitive retardation and reduced stress coping in rats from ancestral stress lines, but not in rats from unstressed lines (Faraji et al 2017 ). In mice, postnatal trauma of unpredictable maternal separation and maternal stress altered coping behaviours in adverse conditions both in males when adult, and in their adult male offspring.…”