Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Abstract

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc−/−) and their wild type (Hdc+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc−/−and Hdc+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc+/+ mice as histamine deficiency prevented almost all of the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.

Molecular underpinnings of programming by early-life stress and the protective effects of early dietary ω6/ω3 ratio, basally and in response to LPS: hippocampal mRNA-miRNAs integrated approach

“…We confirm the previously reported ELS induced cognitive impairments in adult mice fed the high ω6/ω3 diet early in life and the rescue by the low ω6/ω3 diet from P2 until P42 20 . Our results are also in line with the evidence supporting that ω3 fatty acids are important for cognitive functioning in rodents 37,38,68,69 , and that specifically adequate ω3 fatty acid availability during early sensitive stages of development is critical for later life cognitive outcome 26,70 . Our data supports the notion that a relatively short and subtle modulation of the ω6/ω3 ratio during early-life can protect against ELS-induced cognitive deficits in adulthood.…”

“…These beneficial effects of the diet on cognition were associated with a prevention of the ELS-induced changes in survival of hippocampal new-born neurons and microglial CD68 expression. In line with our findings, others have also reported dietary interventions with PUFA’s to be protective against ELS-induced changes in anxiety behaviours and cognitive functions in female rats 37 and during adolescence 38 . Nonetheless currently, the molecular mechanisms underlying the protective effects of these diets are not yet understood.…”

New β-arylchalcogeno amines with procognitive properties targeting Carbonic Anhydrases and Monoamine Oxidases

“…Retention tests were performed after 24 or 48 h, when the subject mouse was presented to a novel object or a novel social stimulus along with those encountered in the previous session. The inter-trial intervals were chosen based on our previous experiences, since at this time-points the control animals are normally unable to discriminate between novel and familiar stimuli [27][28][29]. This experimental design represents an advantage when investigating the intrinsic memory-promoting potential of new compounds because exploiting natural forgetting avoids the use of amnesic drugs, thus ruling out issues related to possible pharmacokinetic interactions [30].…”

Dietary Long-Chain n-3 Polyunsaturated Fatty Acid Supplementation Alters Electrophysiological Properties in the Nucleus Accumbens and Emotional Behavior in Naïve and Chronically Stressed Mice

“…The potential antidepressant effect of EPA was also demonstrated in animal models of depression, such as olfactory bulbectomized rats [ 13 ], chronic unpredictable mild stress [ 14 ], maternal stress [ 15 ], or chronic social defeat stress (CSDS) [ 16 ]. In particular, we previously demonstrated that a dietary intervention with a diet enriched with LC n-3 PUFA (10% EPA and 7% DHA of total fatty acids, see [ 17 ]) partially protected mice from CSDS-induced emotion behavior alteration [ 16 , 18 ]. Altogether, these data suggest that a dietary supplementation with EPA/DHA with a higher proportion of EPA could be efficient to improve symptoms in MDD, however the mechanisms involved are still poorly known.…”

“…Indeed, it has been shown that LC n-3 PUFA dietary supplementation reduces inflammatory processes, including in the brain [ 19 , 20 ], hypothalamic–pituitary–adrenal (HPA) axis alteration [ 5 , 21 , 22 , 23 , 24 ], apical dendritic tree alterations [ 16 ], and promotes neurogenesis [ 25 ], which are altered in depression [ 14 ]. Although there is a close link between n-3 PUFA, synaptic plasticity, and depressive-like symptoms [ 6 , 18 , 26 , 27 ], the effect of EPA/DHA supplementation on synaptic plasticity has been poorly studied. Furthermore, whether EPA/DHA supplementation can restore the synaptic deficit observed in animal models of depression remains to be elucidated.…”