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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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Related in: MedlinePlus

Dietary n-3 PUFA supplementation prevents chronic stress phenotype in mice. (a) Experimental timeline. Social defeat was conducted once a day for 10 days before behaviours on control diet (white) and n-3-supplemented (yellow) mice. n-3 PUFA supplementation (b) failed to reduce number of social exploration (interaction: F1,30=6.305, P=0.0177, two-way ANOVA; **P<0.01; ***P<0.001, Bonferroni's test, n=8–9 per group) but prevented (c) anxiety-like behaviour induced by social defeat (interaction: F1,30=6.012, P<0.05, Two-way ANOVA; *P<0.05; **P<0.01, Bonferroni's test, n=8–9 per group), (d, e) simplification of apical dendritic tree on pyramidal neurons of the dlPFC (interaction: F1,54=4.201, P<0.05, two-way ANOVA; *P<0.05; ***P<0.001, Bonferroni's test, n=14 neurons per group) and dmPFC (interaction: F1,60=7.260, P<0.01, two-way ANOVA; ***P<0.001, Bonferroni's test, n=16 neurons per group) and (f) total corticosterone elevation (interaction: F1,24=4.144, P=0.05, two-way ANOVA; *P<0.05, Bonferroni's test, n=7 per group). Data are displayed as mean±s.e.m.
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fig5: Dietary n-3 PUFA supplementation prevents chronic stress phenotype in mice. (a) Experimental timeline. Social defeat was conducted once a day for 10 days before behaviours on control diet (white) and n-3-supplemented (yellow) mice. n-3 PUFA supplementation (b) failed to reduce number of social exploration (interaction: F1,30=6.305, P=0.0177, two-way ANOVA; **P<0.01; ***P<0.001, Bonferroni's test, n=8–9 per group) but prevented (c) anxiety-like behaviour induced by social defeat (interaction: F1,30=6.012, P<0.05, Two-way ANOVA; *P<0.05; **P<0.01, Bonferroni's test, n=8–9 per group), (d, e) simplification of apical dendritic tree on pyramidal neurons of the dlPFC (interaction: F1,54=4.201, P<0.05, two-way ANOVA; *P<0.05; ***P<0.001, Bonferroni's test, n=14 neurons per group) and dmPFC (interaction: F1,60=7.260, P<0.01, two-way ANOVA; ***P<0.001, Bonferroni's test, n=16 neurons per group) and (f) total corticosterone elevation (interaction: F1,24=4.144, P=0.05, two-way ANOVA; *P<0.05, Bonferroni's test, n=7 per group). Data are displayed as mean±s.e.m.

Mentions: As we show that both social defeat stress and dietary n-3 PUFA deficiency induce HPA axis hyperactivity, we wondered whether n-3 PUFA supplementation that normalises HPA axis activity in chronically stressed rats26 could attenuate the effects of chronic social defeat stress on emotional behaviour (Figure 5a). Increase in corticosterone levels after defeat in control diet mice was completely prevented by chronic dietary n-3 PUFA supplementation (Figure 5f). Although chronic dietary n-3 PUFA supplementation failed to reduce social avoidance after defeat (Figure 5b), it was sufficient to attenuate social defeat-induced anxiety-like behaviour (Figure 5c). Moreover, complexity of neuronal dendrites in both dlPFC and dmPFC of defeated n-3-supplemented mice was similar to that observed in undefeated n-3-supplemented mice (Figures 5d and e). Collectively, after social defeat stress, n-3-supplemented mice showed significant resilience to the effects of social defeat on behaviour, dendritic arborisation in the PFC and HPA axis activity. Hence, it is possible to attenuate chronic stress-induced emotional impairment through n-3 PUFA supplementation that prevents HPA axis hyperactivity and neuronal atrophy in the PFC.


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)

Dietary n-3 PUFA supplementation prevents chronic stress phenotype in mice. (a) Experimental timeline. Social defeat was conducted once a day for 10 days before behaviours on control diet (white) and n-3-supplemented (yellow) mice. n-3 PUFA supplementation (b) failed to reduce number of social exploration (interaction: F1,30=6.305, P=0.0177, two-way ANOVA; **P<0.01; ***P<0.001, Bonferroni's test, n=8–9 per group) but prevented (c) anxiety-like behaviour induced by social defeat (interaction: F1,30=6.012, P<0.05, Two-way ANOVA; *P<0.05; **P<0.01, Bonferroni's test, n=8–9 per group), (d, e) simplification of apical dendritic tree on pyramidal neurons of the dlPFC (interaction: F1,54=4.201, P<0.05, two-way ANOVA; *P<0.05; ***P<0.001, Bonferroni's test, n=14 neurons per group) and dmPFC (interaction: F1,60=7.260, P<0.01, two-way ANOVA; ***P<0.001, Bonferroni's test, n=16 neurons per group) and (f) total corticosterone elevation (interaction: F1,24=4.144, P=0.05, two-way ANOVA; *P<0.05, Bonferroni's test, n=7 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

fig5: Dietary n-3 PUFA supplementation prevents chronic stress phenotype in mice. (a) Experimental timeline. Social defeat was conducted once a day for 10 days before behaviours on control diet (white) and n-3-supplemented (yellow) mice. n-3 PUFA supplementation (b) failed to reduce number of social exploration (interaction: F1,30=6.305, P=0.0177, two-way ANOVA; **P<0.01; ***P<0.001, Bonferroni's test, n=8–9 per group) but prevented (c) anxiety-like behaviour induced by social defeat (interaction: F1,30=6.012, P<0.05, Two-way ANOVA; *P<0.05; **P<0.01, Bonferroni's test, n=8–9 per group), (d, e) simplification of apical dendritic tree on pyramidal neurons of the dlPFC (interaction: F1,54=4.201, P<0.05, two-way ANOVA; *P<0.05; ***P<0.001, Bonferroni's test, n=14 neurons per group) and dmPFC (interaction: F1,60=7.260, P<0.01, two-way ANOVA; ***P<0.001, Bonferroni's test, n=16 neurons per group) and (f) total corticosterone elevation (interaction: F1,24=4.144, P=0.05, two-way ANOVA; *P<0.05, Bonferroni's test, n=7 per group). Data are displayed as mean±s.e.m.
Mentions: As we show that both social defeat stress and dietary n-3 PUFA deficiency induce HPA axis hyperactivity, we wondered whether n-3 PUFA supplementation that normalises HPA axis activity in chronically stressed rats26 could attenuate the effects of chronic social defeat stress on emotional behaviour (Figure 5a). Increase in corticosterone levels after defeat in control diet mice was completely prevented by chronic dietary n-3 PUFA supplementation (Figure 5f). Although chronic dietary n-3 PUFA supplementation failed to reduce social avoidance after defeat (Figure 5b), it was sufficient to attenuate social defeat-induced anxiety-like behaviour (Figure 5c). Moreover, complexity of neuronal dendrites in both dlPFC and dmPFC of defeated n-3-supplemented mice was similar to that observed in undefeated n-3-supplemented mice (Figures 5d and e). Collectively, after social defeat stress, n-3-supplemented mice showed significant resilience to the effects of social defeat on behaviour, dendritic arborisation in the PFC and HPA axis activity. Hence, it is possible to attenuate chronic stress-induced emotional impairment through n-3 PUFA supplementation that prevents HPA axis hyperactivity and neuronal atrophy in the PFC.

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