title: Folic acid prevents depressive-like behavior and hippocampal antioxidant imbalance induced by restraint stress in mice.
abstract: Experimental and epidemiological studies have shown the close relationship between stressful events, depression, and cognitive impairment. Folic acid has been reported to present antidepressant-like effects in both experimental and clinical approaches. However, the mechanisms mediating such effects are not understood. In the present study, we evaluated if folic acid administration to mice could protect against restraint stress-induced depressive-like behavior and cognitive deficit. Considering that oxidative stress has been pointed as a key event involved with depressive disorders, cerebrocortical and hippocampal oxidative stress-related parameters, such as the activities of antioxidant enzymes (mainly those related to the hydroperoxide-detoxifying system) and markers of lipid peroxidation, were also investigated. Restraint stress induced depressive-like behavior in the forced swimming test and memory impairment in the object recognition test, without altering locomotor activity of mice. Folic acid (50 mg/kg, p.o.) was able to prevent the stress-induced increase on immobility time in the forced swimming test, but did not prevent memory impairment. Moreover, restraint stress increased thiobarbituric acid reactive substance levels, and catalase, glutathione peroxidase and glutathione reductase activities in the cerebral cortex and hippocampus, and superoxide dismutase activity in the hippocampus. Folic acid treatment restored the activity of the antioxidant enzymes and reduced lipid peroxidation in the hippocampus. Glutathione, a non-enzymatic antioxidant, was not altered by stress and/or folic acid administration. Together, the results of the present work reinforce the notion that folic acid displays a specific antidepressant profile in the restraint stress paradigm that may be at least partly due to its antioxidant role.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil. jobudni@yahoo.com.br
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.forename: Andréa Dias
authors.initials: AD
authors.lastname: Zomkowski
authors.forename: Daiane
authors.initials: D
authors.lastname: Engel
authors.forename: Danúbia Bonfanti
authors.initials: DB
authors.lastname: Santos
authors.forename: Alessandra Antunes
authors.initials: AA
authors.lastname: dos Santos
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Felipe
authors.initials: F
authors.lastname: Ornell
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000009:adverse effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005492:Folic Acid / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012149:Restraint, Physical / Q000009:adverse effects*; D013315:Stress, Psychological / Q000209:etiology* / Q000378:metabolism / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D005492:Folic Acid