title: Early micronutrient supplementation protects against early stress-induced cognitive impairments.
abstract: Early-life stress (ES) impairs cognition later in life. Because ES prevention is problematic, intervention is needed, yet the mechanisms that underlie ES remain largely unknown. So far, the role of early nutrition in brain programming has been largely ignored. Here, we demonstrate that essential 1-carbon metabolism-associated micronutrients (1-CMAMs; i.e., methionine and B vitamins) early in life are crucial in programming later cognition by ES. ES was induced in male C57Bl/6 mice from postnatal d (P)2-9. 1-CMAM levels were measured centrally and peripherally by using liquid chromatography-mass spectroscopy. Next, we supplemented the maternal diet with 1-CMAM only during the ES period and studied cognitive, neuroendocrine, neurogenic, transcriptional, and epigenetic changes in adult offspring. We demonstrate that ES specifically reduces methionine in offspring plasma and brain. Of note, dietary 1-CMAM enrichment during P2-9 restored methionine levels and rescued ES-induced adult cognitive impairments. Beneficial effects of this early dietary enrichment were associated with prevention of the ES-induced rise in corticosterone and adrenal gland hypertrophy did not involve changes in maternal care, hippocampal volume, neurogenesis, or global/Nr3c1-specific DNA methylation. In summary, nutrition is important in brain programming by ES. A short, early supplementation with essential micronutrients can already prevent lasting effects of ES. This concept opens new avenues for nutritional intervention.-Naninck, E. F. G., Oosterink, J. E., Yam, K.-Y., de Vries, L. P., Schierbeek, H., van Goudoever, J. B., Verkaik-Schakel, R.-N., Plantinga, J. A., Plosch, T., Lucassen, P. J., Korosi, A. Early micronutrient supplementation protects against early stress-induced cognitive impairments.
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors: Eva F G
authors: EF
authors: Naninck
authors: Department of Mother and Child, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors: J Efraim
authors: JE
authors: Oosterink
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors: Kit-Yi
authors: KY
authors: Yam
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors: Lennart P
authors: LP
authors: de Vries
authors: Department of Mother and Child, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors: Henk
authors: H
authors: Schierbeek
authors: Department of Mother and Child, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors: Johannes B
authors: JB
authors: van Goudoever
authors: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Rikst-Nynke
authors: RN
authors: Verkaik-Schakel
authors: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Josèe A
authors: JA
authors: Plantinga
authors: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Torsten
authors: T
authors: Plosch
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors: Paul J
authors: PJ
authors: Lucassen
authors: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands; a.korosi@uva.nl.
authors: Aniko
authors: A
authors: Korosi
mesh_terms: D000375:Aging; D000818:Animals; D060825:Cognitive Dysfunction / Q000209:etiology / Q000517:prevention & control*; D003345:Corticosterone / Q000378:metabolism; D004032:Diet / Q000662:veterinary*; D019587:Dietary Supplements; D005260:Female; D006799:Housing, Animal; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018977:Micronutrients / Q000008:administration & dosage*; D011897:Random Allocation; D013312:Stress, Physiological; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018977:Micronutrients; D014803:Vitamin B Complex; D008715:Methionine; D003345:Corticosterone
keywords: 1-carbon metabolism; HPA-axis; cognition; hippocampus; limited nesting material