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Behav Brain Res. 2014 Mar 15;261:8-16. doi: 10.1016/j.bbr.2013.11.047. Epub 2013 Dec 9.

Behavioral and neurochemical effects of dietary methyl donor deficiency combined with unpredictable chronic mild stress in rats.

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  • 1Laboratoire de Nutrition Génétique et Exposition aux Risques Environnementaux, INSERM U954, Faculté de Médecine de Nancy - UHP, Vandœuvre-lès-Nancy, France; ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France; Clinical Pharmacy Service - Mental Health Establishment (EPSAN), Brumath, France. Electronic address: herve.javelot@ch-epsan.fr.
  • 2ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France.
  • 3Laboratoire de Nutrition Génétique et Exposition aux Risques Environnementaux, INSERM U954, Faculté de Médecine de Nancy - UHP, Vandœuvre-lès-Nancy, France.
  • 4Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7363, Université de Strasbourg, CNRS, Strasbourg, France.
  • 5Laboratoire de Nutrition Génétique et Exposition aux Risques Environnementaux, INSERM U954, Faculté de Médecine de Nancy - UHP, Vandœuvre-lès-Nancy, France; Laboratoire de Microscopie Electronique, Faculté de Médecine de Nancy - UHP, Vandœuvre-lès-Nancy, France.
  • 6Université de Rouen, Dépt. Psychologie, Laboratoire ICONES (EA 4699), Mont-Saint-Aignan, France.

Abstract

Methyl donor deficiencies and chronic stress cause depression independently, but their interaction has never been thoroughly evaluated. In our study, methyl donor deficient diet and chronic stress condition consisted respectively of a B2, B9, B12, and choline-free diet and a chronic mild stress procedure. Rats were randomly assigned to six groups with three "diet" conditions (free-feeding, pair-fed and methyl donor deficient diet) and two "stress" conditions (no-stress and stress) and were evaluated in the open-field, the elevated plus-maze and the forced swimming test. After the behavioral evaluation, corticosterone and homocysteine plasma levels were measured and dopamine, DOPAC, serotonin, 5HIAA concentrations were evaluated in several brain areas. Rats given a methyl donor deficient diet for 11 weeks causing elevated plasma homocysteine levels were compared to pair-fed and free-feeding rats with or without unpredictable chronic mild stress. Regardless of stress environmental conditions, the methyl donor deficient diet decreased plasma corticosterone levels and caused disinhibition in the elevated plus-maze condition relative to both control groups. However, stress potentiated the effects of the deficient regimen on rearing in the open-field and climbing in the forced swim test. The dietary changes involved in behavior and plasma corticosterone could be caused by homocysteine-induced decreases in dopamine and 5-hydroxytryptamine metabolites in selective brain regions and it can be noted that regardless of stress-conditions, methyl donor deficient diet decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus and selectively 5HIAA/serotonin ratio in the sensorimotor cortex. Our experimental data is particularly relevant in the context of neuropsychiatric disorders frequently associated with folate deficiency and hyperhomocysteinemia.

Copyright © 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

B-vitamin; Behavior; Chronic mild stress; Depression; Methyl donors; Rat

PMID:
24333542
[PubMed - indexed for MEDLINE]
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