Trans-generational effects of early life stress: the role of maternal behavior.
Using a rodent paradigm of early life stress, infant maternal separation (IMS), we examined whether IMS-triggered behavioral and epigenetic phenotypes of the stress-susceptible mouse strain Balb/c are propagated across generations. These phenotypes include impaired emotional behavior and deficits in executive cognitive functions in adulthood, and they are associated with increased acetylation of histone H4K12 protein (acH4K12) in the forebrain neocortex. These behavioral and epigenetic phenotypes are transmitted to the first progeny of IMS Balb/c mothers, but not fathers, and cross-fostering experiments revealed that this transmission is triggered by maternal behavior and modulated by the genetic background of the pups. In the continued absence of the original stressor, this transmission fades in later progenies. An adolescent treatment that lowers the levels of acH4K12 in IMS Balb/c mice augments their emotional abnormality but abolishes their cognitive deficits. Conversely, a treatment that further elevates the levels of acH4K12 improved the emotional phenotype but had no effects on the cognitive deficits. Moreover, treatments that prevent the emergence of either emotional or cognitive deficits in the mother also prevent the establishment of such deficits in her offspring, indicating that trans-generational effects of early life stress can be prevented.
1] Department of Psychiatry and Molecular Therapeutics, Columbia University [2] New York State Psychiatric Institute, New York, NY 10032.
Claudia
C
Schmauss
Department of Psychiatry and Molecular Therapeutics, Columbia University.
Zoe
Z
Lee-McDermott
Department of Psychiatry and Molecular Therapeutics, Columbia University.
Liorimar Ramos
LR
Medina
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D003071:Cognition; D004644:Emotions; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D008297:Male; D008425:Maternal Behavior; D008426:Maternal Deprivation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D013315:Stress, Psychological / Q000235:genetics; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology
D006657:Histones; D013806:Theophylline; D043802:GTP-Binding Protein alpha Subunits, Gq-G11