title: Behavioral and neurochemical effects of dietary methyl donor deficiency combined with unpredictable chronic mild stress in rats.
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.
authors: Laboratoire 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.
authors: H
authors: H
authors: Javelot
authors: ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France.
authors: M
authors: M
authors: Messaoudi
authors: Laboratoire de Nutrition Génétique et Exposition aux Risques Environnementaux, INSERM U954, Faculté de Médecine de Nancy - UHP, Vandœuvre-lès-Nancy, France.
authors: C
authors: C
authors: Jacquelin
authors: ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France.
authors: J F
authors: JF
authors: Bisson
authors: ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France.
authors: P
authors: P
authors: Rozan
authors: ETAP-Applied Ethology - Neuropsychopharmacology Department, Vandœuvre-lès-Nancy, France.
authors: A
authors: A
authors: Nejdi
authors: Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7363, Université de Strasbourg, CNRS, Strasbourg, France.
authors: C
authors: C
authors: Lazarus
authors: Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7363, Université de Strasbourg, CNRS, Strasbourg, France.
authors: J C
authors: JC
authors: Cassel
authors: Laboratoire 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.
authors: C
authors: C
authors: Strazielle
authors: Université de Rouen, Dépt. Psychologie, Laboratoire ICONES (EA 4699), Mont-Saint-Aignan, France.
authors: R
authors: R
authors: Lalonde
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002796:Choline Deficiency / Q000150:complications* / Q000378:metabolism*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005494:Folic Acid Deficiency / Q000150:complications* / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood; D018782:Maze Learning / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology* / Q000473:pathology; D013550:Swimming / Q000523:psychology
chemical_list: D001679:Biogenic Amines; D006710:Homocysteine; D003345:Corticosterone
keywords: B-vitamin; Behavior; Chronic mild stress; Depression; Methyl donors; Rat