Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016;2016:8574830.
doi: 10.1155/2016/8574830. Epub 2015 Dec 30.

Nutritional Omega-3 Deficiency Alters Glucocorticoid Receptor-Signaling Pathway and Neuronal Morphology in Regionally Distinct Brain Structures Associated With Emotional Deficits

Affiliations
Free PMC article

Nutritional Omega-3 Deficiency Alters Glucocorticoid Receptor-Signaling Pathway and Neuronal Morphology in Regionally Distinct Brain Structures Associated With Emotional Deficits

Thomas Larrieu et al. Neural Plast. .
Free PMC article

Abstract

Extensive evidence suggests that long term dietary n-3 polyunsaturated fatty acids (PUFAs) deficiency results in altered emotional behaviour. We have recently demonstrated that n-3 PUFAs deficiency induces emotional alterations through abnormal corticosterone secretion which leads to altered dendritic arborisation in the prefrontal cortex (PFC). Here we show that hypothalamic-pituitary-adrenal (HPA) axis feedback inhibition was not compromised in n-3 deficient mice. Rather, glucocorticoid receptor (GR) signaling pathway was inactivated in the PFC but not in the hippocampus of n-3 deficient mice. Consequently, only dendritic arborisation in PFC was affected by dietary n-3 PUFAs deficiency. In addition, occlusion experiment with GR blockade altered GR signaling in the PFC of control mice, with no further alterations in n-3 deficient mice. In conclusion, n-3 PUFAs deficiency compromised PFC, leading to dendritic atrophy, but did not change hippocampal GR function and dendritic arborisation. We argue that this GR sensitivity contributes to n-3 PUFAs deficiency-related emotional behaviour deficits.

Figures

Figure 1
Figure 1
Effects of n-3 deficient diet on total plasma corticosterone levels. N-3 deficient mice showed total corticosterone elevation as compared to control diet mice in steady-state condition (t 7 = 2.472, p < 0.05, unpaired t-test, n = 4-5 per group). Data are displayed as mean ± SEM.
Figure 2
Figure 2
Corticosterone levels after dexamethasone application. (a) Experimental timeline. The mice received a single intraperitoneal injection of dexamethasone dissolved in saline or NaCl 6 hours before decapitation and determination of total corticosterone levels in plasma. (b) A significant interaction between diet and treatment was revealed on corticosterone suppression (interaction: F 1,22 = 12.58, p < 0.01, two-way ANOVA, Bonferroni's test; n = 6-7 per group). After administration of dexamethasone both control diet and n-3 deficient mice showed decreased corticosterone levels in plasma. Data are displayed as mean ± SEM.
Figure 3
Figure 3
Effects of n-3 deficient diet on GR signaling pathway and emotional behaviours. (a) Experimental timeline. Mifepristone pellets released continuously 20 mg/kg/day for 21 days. After 21 days of treatment, open-field and social interaction tests were performed. One day after the last behavioural test, mice were sacrificed for Western blot analysis. (b, c) A significant interaction between diet and treatment was revealed on both (b) GR (interaction: F 1,14 = 5.540, p < 0.05, two-way ANOVA, Bonferroni's test; n = 4-5 per group) and (c) FKBP51 expression in the PFC (interaction: F 1,17 = 7.584, p < 0.05, two-way ANOVA, Bonferroni's test; n = 4-5 per group). (d) No change was revealed in the expression of E6AP in the PFC of mice (interaction: F 1,21 = 0.9281, p = 0.3463, diet effect: F 1,21 = 0.1845, p = 0.6719, treatment effect: F 1,21 = 0.07035, p = 0.7934, two-way ANOVA; n = 6-7 per group). (e) Mifepristone effect on GR occurred in the HC regardless of the diet condition (treatment effect: F 1,17 = 5.991, p < 0.05, two-way ANOVA; n = 4-5 per group). (f) A significant interaction between diet and treatment was revealed on FKBP51 expression in the hippocampus (interaction: F 1,16 = 4.631, p < 0.05, two-way ANOVA, Bonferroni's test; n = 4 per group). (g) The expression of E6AP in the HC of n-3 deficient mice was reduced as compared to control diet mice whatever the treatment (interaction: F 1,20 = 0.3197, p = 0.5781, diet effect: F 1,20 = 4.571, p = 0.0451, treatment effect: F 1,20 = 1.250, p = 0.2769, two-way ANOVA; n = 5–7 per group). A significant interaction between diet and treatment was revealed on both (h) social interaction (interaction: F 1,31 = 16.27, p < 0.001, two-way ANOVA, Bonferroni's test; n = 8–10 per group) and (i) open-field test (interaction: F 1,38 = 7.309, p < 0.05, two-way ANOVA, Bonferroni's test; n = 10-11 per group). Data are displayed as mean ± SEM. # p < 0.09; p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001.
Figure 4
Figure 4
Effect of maternal n-3 deficient diet on dendritic arborisation in the PFC and hippocampus. (a, b, c left) dlPFC, dmPFC, and dorsal CA1 regions are represented. N-3 deficient diet induced shrinking of apical dendritic arborisation on pyramidal neurons of dlPFC (t 28 = 3.323, ∗∗ p < 0.01, unpaired t-test, n = 15 neurons per group) and of dmPFC (t 34 = 4.125, ∗∗∗ p < 0.001, unpaired t-test, n = 16 neurons per group). Dietary n-3 PUFAs deficient diet did not alter dendritic arborisation in the dorsal CA1 of the hippocampus (t 25 = 1.791, p > 0.05, unpaired t-test, n = 14 neurons per group). Data are displayed as mean ± SEM.

Similar articles

See all similar articles

Cited by 4 articles

References

    1. Lafourcade M., Larrieu T., Mato S., et al. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nature Neuroscience. 2011;14(3):345–350. doi: 10.1038/nn.2736. - DOI - PubMed
    1. Maccari S., Morley-Fletcher S. Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendocrinology. 2007;32(supplement 1):S10–S15. doi: 10.1016/j.psyneuen.2007.06.005. - DOI - PubMed
    1. Cao D., Kevala K., Kim J., et al. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. Journal of Neurochemistry. 2009;111(2):510–521. doi: 10.1111/j.1471-4159.2009.06335.x. - DOI - PMC - PubMed
    1. Hibbeln J. R. Fish consumption and major depression. The Lancet. 1998;351(9110):p. 1213. doi: 10.1016/s0140-6736(05)79168-6. - DOI - PubMed
    1. Simopoulos A. P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy. 2002;56(8):365–379. - PubMed

Publication types

Substances

LinkOut - more resources

Feedback