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

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.

Dietary Omega-6/Omega-3 and Endocannabinoids: Implications for Brain Health and Diseases

“…Indeed, dietary PUFAs are powerful modulators of the HPA axis, and function of endocannabinoids is also tightly related to the HPA axis. Our studies demonstrated that variations in dietary ω-3 PUFAs impact on the HPA axis [136,151]: mice fed with an ω-3 PUFA deficient diet exhibit higher levels of corticosterone while mice fed with a DHA rich diet display control levels of corticosterone, and these levels are not affected by social defeat stress. In parallel, interactions between endocannabinoids and the HPA axis are reciprocal.…”

“…The clinical studies are corroborated by preclinical studies. Dietary ω-3 deficiency in rodents induces strong anxiety-and depressive-like behaviors [7-9, [135][136][137]. Conversely, ω-3 supplementation given beforehand a protocol of acute or chronic stress plays a protective role against anxiety-and depressive-like behaviors [136,138,139].…”

“…From these studies, it thus appears that both dietary PUFAs and endocannabinoids play a role in mood and anxiety disorders and the link between both has been made only in our laboratory in preclinical studies. We demonstrated that an ω-3 deficient diet from the first gestational stage greatly impairs endocannabinoid signaling, which is associated to anxiety and depressive-like behaviors in mice [7,136]. Currently, our ongoing studies tend to demonstrate that DHA-rich diet protects mice from deleterious effects of a chronic social defeat stress on anxiety-and depressive-like behaviors and on endocannabinoid-dependent synaptic plasticity.…”

n-3 PUFAs have beneficial effects on anxiety and cognition in female rats: Effects of early life stress

“…Furthermore, the abundance and activity of GRs is linked with the functionality of the HPA, the dysregulation of which is implicated with maladaptive responses to the stress (Pariante, 2009). Supplementation of n-3 PUFAs has been shown to impede the disruption of normal HPA functionality associated with the development of neuropsychiatric disorders (Larrieu et al, 2014). Moreover, n-3 PUFAs, among their biological properties, have shown anti-inflammatory effects as a possible pathway through which they can be effective both in preventing or treating stress related disorders (Grosso et al, 2014).…”

Altered serum fatty acid composition in geriatric depression

“…In addition, the immunosuppressive effects of n-3 PUFAs and their impacts on p-glycoprotein may affect the pathophysiology of geriatric depression (Murck et al 2004;Yusof et al 2008). Moreover, the impact of FA on the development of geriatric depression could rely on the induction of chronic stress, reflected by disrupted glucocorticoid receptor-mediated signalling pathway along with hypothalamic-pituitary-adrenal axis hyperactivity as recently reported (Larrieu et al 2014). This hyperactivity leads to neuronal atrophy in specific brain areas and subsequent depression-related behavioural changes.…”