title: Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour.
abstract: Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDL-cholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain.
authors.affiliation: Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Paternain
authors.affiliation: Department of Pharmacology and Toxicology, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martisova
authors.affiliation: Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health Institute, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Campión
authors.affiliation: Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health Institute, Madrid, Spain; IDISNA, Navarra's Health Research Institute, Pamplona, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Pharmacology and Toxicology, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain; IDISNA, Navarra's Health Research Institute, Pamplona, Spain. Electronic address: mariaja@unav.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramírez
authors.affiliation: Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health Institute, Madrid, Spain.
authors.forename: Fermin I
authors.initials: FI
authors.lastname: Milagro
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol; D019175:DNA Methylation / Q000187:drug effects; D003863:Depression / Q000178:diet therapy*; D019587:Dietary Supplements; D004435:Eating; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007774:Lactation; D008426:Maternal Deprivation; D051381:Rats; D011972:Receptor, Insulin; D013315:Stress, Psychological; D015430:Weight Gain
chemical_list: D002784:Cholesterol; D011972:Receptor, Insulin
keywords: Cholesterol; DNA methylation; Hippocampus; Insulin receptor; NORT; Porsolt; Stress