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Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion.

Larrieu T, Hilal ML, Hilal LM, Fourrier C, De Smedt-Peyrusse V, Sans N, N S, Capuron L, Layé S - Transl Psychiatry (2014)

Bottom Line: This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress.Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity.These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

View Article: PubMed Central - PubMed

Affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Universite de Bordeaux, Nutrition et Neurobiologie intégrée, UMR 1286, Bordeaux, France.

ABSTRACT
Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

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Corticosterone synthesis inhibitor blunts depressive-like behaviour in forced swimming test in n-3-deficient mice. n-3-deficient mice displayed (b) reduced swimming occurrence as compared with control diet mice. Metyrapone administration (75 mg kg−1) 90 min before forced swimming test prevented depressive-like behaviour in n-3-deficient mice (interaction: F1,27=7.486, P<0.05, two-way ANOVA; **P<0.01, Bonferroni's test, n=7–8 per group) that was not due to (a) locomotor activity changes (interaction: F1,27=1.407, P>0.05, diet effect: F1,27=1.795, P>0.05, treatment effect: F1,27=0.06567, P>0.05, two-way ANOVA, n=7–8 per group). Data are displayed as mean±s.e.m.
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fig4: Corticosterone synthesis inhibitor blunts depressive-like behaviour in forced swimming test in n-3-deficient mice. n-3-deficient mice displayed (b) reduced swimming occurrence as compared with control diet mice. Metyrapone administration (75 mg kg−1) 90 min before forced swimming test prevented depressive-like behaviour in n-3-deficient mice (interaction: F1,27=7.486, P<0.05, two-way ANOVA; **P<0.01, Bonferroni's test, n=7–8 per group) that was not due to (a) locomotor activity changes (interaction: F1,27=1.407, P>0.05, diet effect: F1,27=1.795, P>0.05, treatment effect: F1,27=0.06567, P>0.05, two-way ANOVA, n=7–8 per group). Data are displayed as mean±s.e.m.

Mentions: To test whether HPA axis hyperactivity is responsible for dietary n-3 PUFA deficiency-induced emotional impairment, we clamped the HPA axis output by adrenalectomy followed by low corticosterone replacement19 (Adx groups; Figure 3a). In the absence of high corticosterone levels, Adx n-3-deficient mice exhibited an increase in the number of social exploration and in the time spent exploring the centre of an open field compared with sham-operated n-3-deficient mice. In addition, complexity of neuronal arborisation in the dlPFC and dmPFC was higher in Adx n-3-deficient mice than sham-operated n-3-deficient mice (Figures 3b–e). Adrenalectomy and low corticosterone replacement maintained plasma corticosterone levels in Adx n-3-deficient mice at 50% lower than those measured in sham-operated n-3-deficient mice (Figure 3f). No effect of Adx and low corticosterone replacement was found in control diet mice on all the parameters measured (Supplementary Figure S4). Furthermore, acute administration of a corticosterone synthesis blocker, Metyrapone, reversed despair-like behaviour previously reported in n-3-deficient mice using the forced swimming test11,20 (Figure 4). These data demonstrate that dietary n-3 PUFA deficiency leads to emotional and neuronal impairments through chronic adrenal activation.


Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion.

Larrieu T, Hilal ML, Hilal LM, Fourrier C, De Smedt-Peyrusse V, Sans N, N S, Capuron L, Layé S - Transl Psychiatry (2014)

Corticosterone synthesis inhibitor blunts depressive-like behaviour in forced swimming test in n-3-deficient mice. n-3-deficient mice displayed (b) reduced swimming occurrence as compared with control diet mice. Metyrapone administration (75 mg kg−1) 90 min before forced swimming test prevented depressive-like behaviour in n-3-deficient mice (interaction: F1,27=7.486, P<0.05, two-way ANOVA; **P<0.01, Bonferroni's test, n=7–8 per group) that was not due to (a) locomotor activity changes (interaction: F1,27=1.407, P>0.05, diet effect: F1,27=1.795, P>0.05, treatment effect: F1,27=0.06567, P>0.05, two-way ANOVA, n=7–8 per group). Data are displayed as mean±s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4203007&req=5

fig4: Corticosterone synthesis inhibitor blunts depressive-like behaviour in forced swimming test in n-3-deficient mice. n-3-deficient mice displayed (b) reduced swimming occurrence as compared with control diet mice. Metyrapone administration (75 mg kg−1) 90 min before forced swimming test prevented depressive-like behaviour in n-3-deficient mice (interaction: F1,27=7.486, P<0.05, two-way ANOVA; **P<0.01, Bonferroni's test, n=7–8 per group) that was not due to (a) locomotor activity changes (interaction: F1,27=1.407, P>0.05, diet effect: F1,27=1.795, P>0.05, treatment effect: F1,27=0.06567, P>0.05, two-way ANOVA, n=7–8 per group). Data are displayed as mean±s.e.m.
Mentions: To test whether HPA axis hyperactivity is responsible for dietary n-3 PUFA deficiency-induced emotional impairment, we clamped the HPA axis output by adrenalectomy followed by low corticosterone replacement19 (Adx groups; Figure 3a). In the absence of high corticosterone levels, Adx n-3-deficient mice exhibited an increase in the number of social exploration and in the time spent exploring the centre of an open field compared with sham-operated n-3-deficient mice. In addition, complexity of neuronal arborisation in the dlPFC and dmPFC was higher in Adx n-3-deficient mice than sham-operated n-3-deficient mice (Figures 3b–e). Adrenalectomy and low corticosterone replacement maintained plasma corticosterone levels in Adx n-3-deficient mice at 50% lower than those measured in sham-operated n-3-deficient mice (Figure 3f). No effect of Adx and low corticosterone replacement was found in control diet mice on all the parameters measured (Supplementary Figure S4). Furthermore, acute administration of a corticosterone synthesis blocker, Metyrapone, reversed despair-like behaviour previously reported in n-3-deficient mice using the forced swimming test11,20 (Figure 4). These data demonstrate that dietary n-3 PUFA deficiency leads to emotional and neuronal impairments through chronic adrenal activation.

Bottom Line: This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress.Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity.These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

View Article: PubMed Central - PubMed

Affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Universite de Bordeaux, Nutrition et Neurobiologie intégrée, UMR 1286, Bordeaux, France.

ABSTRACT
Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

Show MeSH
Related in: MedlinePlus