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

Alessia Costa,Conall Strain,Thomaz F S Bastiaanssen,Gustavo Provensi,Clara S Martínez,Francesco Bonfiglio,John F Cryan,Barbara Rani,Moira Rossitto,Marcus Boehme,Sophie Layé,Maria Beatrice Passani,Eoin Gunnigle,Patrizio Blandina,Renato Corradetti

doi:10.3390/ijms23020862

Alessia Costa, Conall Strain + Show 13 more

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https://doi.org/10.3390/ijms23020862

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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 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.

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In our study we used a diet enriched with n-3 LC-PUFAs and vitamin A, a combination of nutrients which we demonstrated being sufficient to prevent the deleterious cognitive decline induced by social instability stress during rats juvenile period [12]
The absence of host histamine synthesis played a key role, abrogating the pro-cognitive actions of the diet, but it prevented the effects of diet on hippocampal neuronal plasticity, hippocampal oxylipin and cytokine profile, and/alongside diet-induced microbiota modifications
One interesting aspect of our results is that chronic stress per se deteriorated the cognitive performance of wild type and histamine-deficient mice ; both genotypes exhibited short-term memory impairment and social avoidance because of the 10 days of social defeat stress

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Repeated exposure to stressful stimuli is a well-known risk factor for the development of anxiety and mood disorders. Chronic stressors are defined as persistent events which require an individual to make adaptations over an extended period. The experienced emotional, behavioural, and physiological toll can predispose an individual to a greater risk of developing mental disorders and physical illness [1]. The majority of human psychopathologies are of a social nature and are associated with cognitive decline [2]. Chronic social stress is a prominent contributor to mood disorder prevalence and suicide creativecommons.org/licenses/by/

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