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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

Glucocorticoid receptors (GR) and GR targets expression is impaired in the PFC of n-3-deficient mice. GR, MR, FKB51 and BDNF proteins expression was measured with western blot analysis in the PFC and the hippocampus of control diet (white) and n-3-deficient mice (red). n-3-deficient mice showed (a) a marked downregulation of GR expression within the PFC as compared with control diet mice (t11=5.659, ***P<0.0001, unpaired t-test, n=6–7 per group). (b) There was no significant effect of n-3 PUFA-deficient diet on either the 70-kDa MR (t12=1.274, P>0.05, unpaired t-test, n=7 per group) or the 102-kDa MR (t12=0.05060, P>0.05, unpaired t-test, n=7 per group) expression within the PFC. GR-dependent target (c) BDNF and (d) FKBP51 expression was significantly reduced in the PFC of n-3-deficient mice as compared with control diet mice (t10=3.671, **P<0.01, unpaired t-test, n=6 per group and t10=3.351, **P<0.01, unpaired t-test, n=6 per group, respectively). There was no effect of dietary n-3 PUFA deficiency on the expression of (e) GR (t11=0.1953, P>0.05, unpaired t-test, n=6–7 per group), (f) 70-kDa MR (t12=1.599, P>0.05, unpaired t-test, n=7 per group), 120-kDa MR (t10=0.8858, P>0.05, unpaired t-test, n=6 per group), (g) GR-dependent target BDNF (t11=1.097, P>0.05, unpaired t-test, n=6–7 per group) and (h) FKBP51 (t8=1.730, P>0.05, unpaired t-test, n=5 per group) in the hippocampus as compared with control diet. Data are displayed as mean±s.e.m.
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fig2: Glucocorticoid receptors (GR) and GR targets expression is impaired in the PFC of n-3-deficient mice. GR, MR, FKB51 and BDNF proteins expression was measured with western blot analysis in the PFC and the hippocampus of control diet (white) and n-3-deficient mice (red). n-3-deficient mice showed (a) a marked downregulation of GR expression within the PFC as compared with control diet mice (t11=5.659, ***P<0.0001, unpaired t-test, n=6–7 per group). (b) There was no significant effect of n-3 PUFA-deficient diet on either the 70-kDa MR (t12=1.274, P>0.05, unpaired t-test, n=7 per group) or the 102-kDa MR (t12=0.05060, P>0.05, unpaired t-test, n=7 per group) expression within the PFC. GR-dependent target (c) BDNF and (d) FKBP51 expression was significantly reduced in the PFC of n-3-deficient mice as compared with control diet mice (t10=3.671, **P<0.01, unpaired t-test, n=6 per group and t10=3.351, **P<0.01, unpaired t-test, n=6 per group, respectively). There was no effect of dietary n-3 PUFA deficiency on the expression of (e) GR (t11=0.1953, P>0.05, unpaired t-test, n=6–7 per group), (f) 70-kDa MR (t12=1.599, P>0.05, unpaired t-test, n=7 per group), 120-kDa MR (t10=0.8858, P>0.05, unpaired t-test, n=6 per group), (g) GR-dependent target BDNF (t11=1.097, P>0.05, unpaired t-test, n=6–7 per group) and (h) FKBP51 (t8=1.730, P>0.05, unpaired t-test, n=5 per group) in the hippocampus as compared with control diet. Data are displayed as mean±s.e.m.

Mentions: High corticosterone levels in n-3-deficient mice prompted us to further investigatethe expression of its receptors (GR and MR) as well as the GR-dependent target BDNF and FKBP51. We observed that exposure to dietary n-3 PUFA deficiency not only affected corticosterone secretion but also disturbed GR-mediated signalling pathway in PFC (Figure 2). Precisely, expressions of GR (Figure 2a) and GR-responsive genes, that is, BDNF (Figure 2c) and FKBP51 (Figure 2d), were downregulated specifically in PFC but not in the hippocampus (Figures 2g and h) of n-3-deficient versus control diet mice. No significant change was revealed in both 70- and 102-kDa MR expressions in the PFC (Figure 2b) or HC (Figure 2f) whatever the group. Collectively, these results show that dietary n-3 PUFA deficiency alone induces neuronal atrophy in the PFC and HPA axis hyperactivity similarly to social defeat stress.


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)

Glucocorticoid receptors (GR) and GR targets expression is impaired in the PFC of n-3-deficient mice. GR, MR, FKB51 and BDNF proteins expression was measured with western blot analysis in the PFC and the hippocampus of control diet (white) and n-3-deficient mice (red). n-3-deficient mice showed (a) a marked downregulation of GR expression within the PFC as compared with control diet mice (t11=5.659, ***P<0.0001, unpaired t-test, n=6–7 per group). (b) There was no significant effect of n-3 PUFA-deficient diet on either the 70-kDa MR (t12=1.274, P>0.05, unpaired t-test, n=7 per group) or the 102-kDa MR (t12=0.05060, P>0.05, unpaired t-test, n=7 per group) expression within the PFC. GR-dependent target (c) BDNF and (d) FKBP51 expression was significantly reduced in the PFC of n-3-deficient mice as compared with control diet mice (t10=3.671, **P<0.01, unpaired t-test, n=6 per group and t10=3.351, **P<0.01, unpaired t-test, n=6 per group, respectively). There was no effect of dietary n-3 PUFA deficiency on the expression of (e) GR (t11=0.1953, P>0.05, unpaired t-test, n=6–7 per group), (f) 70-kDa MR (t12=1.599, P>0.05, unpaired t-test, n=7 per group), 120-kDa MR (t10=0.8858, P>0.05, unpaired t-test, n=6 per group), (g) GR-dependent target BDNF (t11=1.097, P>0.05, unpaired t-test, n=6–7 per group) and (h) FKBP51 (t8=1.730, P>0.05, unpaired t-test, n=5 per group) in the hippocampus as compared with control diet. Data are displayed as mean±s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Glucocorticoid receptors (GR) and GR targets expression is impaired in the PFC of n-3-deficient mice. GR, MR, FKB51 and BDNF proteins expression was measured with western blot analysis in the PFC and the hippocampus of control diet (white) and n-3-deficient mice (red). n-3-deficient mice showed (a) a marked downregulation of GR expression within the PFC as compared with control diet mice (t11=5.659, ***P<0.0001, unpaired t-test, n=6–7 per group). (b) There was no significant effect of n-3 PUFA-deficient diet on either the 70-kDa MR (t12=1.274, P>0.05, unpaired t-test, n=7 per group) or the 102-kDa MR (t12=0.05060, P>0.05, unpaired t-test, n=7 per group) expression within the PFC. GR-dependent target (c) BDNF and (d) FKBP51 expression was significantly reduced in the PFC of n-3-deficient mice as compared with control diet mice (t10=3.671, **P<0.01, unpaired t-test, n=6 per group and t10=3.351, **P<0.01, unpaired t-test, n=6 per group, respectively). There was no effect of dietary n-3 PUFA deficiency on the expression of (e) GR (t11=0.1953, P>0.05, unpaired t-test, n=6–7 per group), (f) 70-kDa MR (t12=1.599, P>0.05, unpaired t-test, n=7 per group), 120-kDa MR (t10=0.8858, P>0.05, unpaired t-test, n=6 per group), (g) GR-dependent target BDNF (t11=1.097, P>0.05, unpaired t-test, n=6–7 per group) and (h) FKBP51 (t8=1.730, P>0.05, unpaired t-test, n=5 per group) in the hippocampus as compared with control diet. Data are displayed as mean±s.e.m.
Mentions: High corticosterone levels in n-3-deficient mice prompted us to further investigatethe expression of its receptors (GR and MR) as well as the GR-dependent target BDNF and FKBP51. We observed that exposure to dietary n-3 PUFA deficiency not only affected corticosterone secretion but also disturbed GR-mediated signalling pathway in PFC (Figure 2). Precisely, expressions of GR (Figure 2a) and GR-responsive genes, that is, BDNF (Figure 2c) and FKBP51 (Figure 2d), were downregulated specifically in PFC but not in the hippocampus (Figures 2g and h) of n-3-deficient versus control diet mice. No significant change was revealed in both 70- and 102-kDa MR expressions in the PFC (Figure 2b) or HC (Figure 2f) whatever the group. Collectively, these results show that dietary n-3 PUFA deficiency alone induces neuronal atrophy in the PFC and HPA axis hyperactivity similarly to social defeat stress.

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