Effect of ALA, EPA, DHA and estrogen on depression in ovariectomized rats

Abstract

Our previous studies showed that n-3 polyunsaturated fatty acids (PUFAs) as well as estrogen had synergistic antidepressant-like effects. The purpose of the present study was to investigate the hypothesis that three major n-3 PUFAs such as α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) individually had antidepressant effects with 17β-estradiol-3-benzoate (E) through neurobiological pathway in ovariectomized (OVX) rats. Rats were fed a modified AIN-93G diet with 0% n-3 PUFAs, and 1% ALA, EPA and DHA relative to the total energy intake during 12 weeks, and injected corn oil or E every 4 days during the last 3 weeks. Supplementation of EPA and DHA and E increased serum concentration of serotonin and climbing, but decreased immobility during forced swimming test. Consistently, supplementation of EPA and DHA and E decreased hippocampal expressions of interleukin-6 and tumor necrosis factor-α, but increased cAMP response element binding protein, brain-derived neurotrophic factor (BDNF) and estrogen receptor-α. Immunofluorescence staining also showed elevated expressions of BDNF. Magnetic resonance spectroscopy showed that E increased glucose, but decreased glutamate, glutamine and myo-inositol concentration regardless of n-3 PUFA supplementation. In addition, supplementation of EPA and DHA and E decreased levels of nitric oxide metabolite However, ALA had no antidepressant effect. The present study suggested that the antidepressant-like effects of EPA and DHA supplementation and E could be due to the regulation of serotonergic neurotransmission and inflammatory cytokines, rather than anti-oxidative system. Supplementation of n-3 PUFA and E had additional function of modulation of neurometabolites in hippocampus.