Epigenetic Transmission of the Impact of Early Stress Across Generations

• Published in: Biological psychiatry (1969) Vol. 68; no. 5; pp. 408 - 415
• Main Authors: Franklin, Tamara B, Russig, Holger, Weiss, Isabelle C, Gräff, Johannes, Linder, Natacha, Michalon, Aubin, Vizi, Sandor, Mansuy, Isabelle M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2010
• Subjects: Age Factors; Animals; Behavior, Animal - physiology; Brain; Brain - metabolism; Brain - pathology; depression; DNA methylation; DNA Methylation - physiology; early stress; Epigenesis, Genetic; epigenetic; Female; Gene Expression; germline; Humans; Male; Maternal Deprivation; Mental Disorders - etiology; Mice; Models, Animal; Psychiatry; Sex Factors; Stress, Psychological - complications; Stress, Psychological - genetics; Stress, Psychological - physiopathology; DNA methylation; Brain; depression; germline; epigenetic; early stress
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2010.05.036

Background Traumatic experiences in early life are risk factors for the development of behavioral and emotional disorders. Such disorders can persist through adulthood and have often been reported to be transmitted across generations. Methods To investigate the transgenerational effect of early stress, mice were exposed to chronic and unpredictable maternal separation from postnatal day 1 to 14. Results We show that chronic and unpredictable maternal separation induces depressive-like behaviors and alters the behavioral response to aversive environments in the separated animals when adult. Most of the behavioral alterations are further expressed by the offspring of males subjected to maternal separation, despite the fact that these males are reared normally. Chronic and unpredictable maternal separation also alters the profile of DNA methylation in the promoter of several candidate genes in the germline of the separated males. Comparable changes in DNA methylation are also present in the brain of the offspring and are associated with altered gene expression. Conclusions These findings highlight the negative impact of early stress on behavioral responses across generations and on the regulation of DNA methylation in the germline.