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

Jamshid Faraji,Nasrin Soltanpour,Reza Moeeini,David M Olson,S Abedin Hosseini,Nabiollah Soltanpour,Gerlinde A S Metz,Hamid Lotfi,Shabnam Roudaki,Ali-Reza Moharreri,Majid H Mohajerani,Ali-Akbar Abdollahi

doi:10.1038/s41598-017-05440-8

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.

Highlights

Recent evidence has shown that the susceptibility to many complex diseases, such as psychiatric disorders, is causally linked to a history of transgenerational adverse experiences[1,2,3,4]
The present study provides the first account of synergistic interactions between two adverse events in female rats with a history of four generations of multigenerational stress
The major findings of this study include the following: (1) gestational prenatal stress can induce cumulative effects that remain silent across four generations and (2) generates a phenotype that is vulnerable to a depression-like state in adulthood when challenged with stress; (3) neither social isolation nor adulthood stress individually unmask the latent neuro-behavioural consequences of ancestral gestational stress in F4 rats; (4) F4 stressed rats that were socially isolated during adulthood stress displayed dysregulation of HPA-axis activity, hippocampal atrophy and psychomotor retardation, a delayed onset of depression-relevant changes induced by synergy between two hits of stress

Summary

Introduction

Recent evidence has shown that the susceptibility to many complex diseases, such as psychiatric disorders, is causally linked to a history of transgenerational adverse experiences[1,2,3,4]. A recent study indicated that cumulative impact by multigenerational prenatal stress may generate new behavioural traits in the F4 generation[20]. Both prenatal and multigenerational stress re-program hypothalamic-pituitary-adrenal (HPA) axis function and may result in increased sensitivity to stress in later life[21, 22]. We proposed that social isolation during stress in adulthood could enhance vulnerability to depression-like outcomes in rats with a history of multigenerational ancestral stress. The result of our experiment suggest that recurrent prenatal stress across generations causes latent (silent) stress vulnerability that becomes overt by interaction of two different stressors in later life, social isolation and restraint stress. Postnatal adversities may synergistically interact to unfold their psychopathological impact on a vulnerable population

Methods

Results

Conclusion