Lasting effects of early life stress in mice: interaction of maternal environment and infant genes

• Published in: Genes, brain and behavior Vol. 16; no. 8; pp. 768 - 780
• Main Authors: Feifel, A. J., Shair, H. N., Schmauss, C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2017; John Wiley & Sons, Inc
• Subjects: Animals; Attention; Brain - metabolism; Brain - physiology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Children; Cognition; Cognitive ability; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; early life stress; Emotions; Epigenesis, Genetic; Epigenetics; F1 hybrid mice; Female; Genetic Background; Histone deacetylase; histone deacetylase 1; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - metabolism; Hybrids; Inbreeding; infant genes; Male; Maternal Behavior; maternal care; Maternal Deprivation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Promoter Regions, Genetic; Rodents; Short term memory; Stress, Psychological - genetics; Stress, Psychological - physiopathology; Transcription Factors - genetics; Transcription Factors - metabolism; infant genes; F1 hybrid mice; cognition; maternal care; early life stress; histone deacetylase 1
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12395

In the mouse, a powerful paradigm of early life stress, infant maternal separation (IMS), can trigger emotional and cognitive dysfunctions in adulthood similar to those found in humans with a history of childhood adversity. The magnitude of IMS effects differs among diverse inbred strains suggesting an interaction between the genetic background of pups and the maternal care they received. Here, we investigated this interaction with studies on reciprocal F1 hybrid mice of the stress‐susceptible Balb/c and the resilient C57Bl/6 strains that were either raised by Balb/c mothers (low maternal care) or by C57Bl/6 mothers (higher maternal care) with or without IMS exposure. The ultrasonic vocalization response to isolation was recorded from infant F1 pups, and their emotional, executive cognitive and epigenetic phenotypes were assessed in adulthood. These studies showed that, regardless of the maternal care received, the emotional phenotype of F1 hybrids was not significantly affected by IMS exposure. However, F1 pups raised by Balb/c (but not C57Bl/6) mothers during IMS exposure exhibit deficits in working memory and attention‐set‐shifting in adulthood. They also exhibit reduced histone deacetylase 1 levels at promotors of brain‐derived neurotrophic factor and early growth response 2 genes, and abnormally high induction of expression of these genes during cognitive testing. As one of affected genes was previously shown to associate with the Balb/c and the other with the C57Bl/6 genetic background, these findings indicate that both parental alleles interact with the maternal environment to modulate the cognitive and epigenetic phenotypes of F1 mice exposed to the IMS. Balb/c × C57Bl/6 F1 mice raised by Balb/c mothers during early life stress have reduced HDAC1 activity at gene promotors and cognitive deficits.