The Anti-Inflammatory Role of Omega-3 Polyunsaturated Fatty Acids Metabolites in Pre-Clinical Models of Psychiatric, Neurodegenerative, and Neurological Disorders.

Juliette Giacobbe,Bonnie Benoiton,Alessandra Borsini,Carmine M Pariante,Patricia Zunszain

doi:10.3389/fpsyt.2020.00122

Juliette Giacobbe, Bonnie Benoiton + Show 3 more

Open Access

https://doi.org/10.3389/fpsyt.2020.00122

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Abstract

Inflammation has been identified as one of the main pathophysiological mechanisms underlying neuropsychiatric and neurodegenerative disorders. Despite the role of inflammation in those conditions, there is still a lack of effective anti-inflammatory therapeutic strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) can reduce depressive symptoms and exert anti-inflammatory action putatively by the production of distinct n-3 PUFA-derived metabolites, such as resolvins D (RvD) and E (RvE) series, maresins (MaR) and protectins (PD), which are collectively named specialized pro-resolving mediators (SPMs) and act as strong anti-inflammatory agents. In this review we summarize evidence showing the effects of treatment with those metabolites in pre-clinical models of psychiatric, neurodegenerative and neurological disorders. A total of 25 pre-clinical studies were identified using the PubMed database. Overall, RvD and RvE treatment improved depressive-like behaviors, whereas protectins and maresins ameliorated neurological function. On a cellular level, RvDs increased serotonin levels in a model of depression, and decreased gliosis in neurodegenerative disorders. Protectins prevented neurite and dendrite retraction and apoptosis in models of neurodegeneration, while maresins reduced cell death across all studies. In terms of mechanisms, all SPMs down-regulated pro-inflammatory cytokines. Resolvins activated mTOR and MAP/ERK signaling in models of depression, while resolvins and maresins activated the NF-κB pathway in models of neurodegeneration and neurological disorders. Our review indicates a potential promising approach for tailored therapy with n-3 PUFAs-derived metabolites in the treatment of psychiatric, neurodegenerative, and neurological conditions.

Highlights

Over the last few decades, inflammation has been identified as one of the main pathophysiological mechanisms underlying psychiatric conditions [1, 2]
Of the review we summarize behavioral, cellular, and molecular outcomes identified in ex vivo, in vivo, and in vitro studies which used treatment with resolvins, protectins and maresins in the context of psychiatric, neurodegenerative, and neurological disorders (Table 1)
Behavioral Findings Models of neurodegenerative and neurological disorders Behavioral effects of PD1 administration were measured in three in vivo studies, one in the context of epilepsy and two in the context of stroke, both conditions which are associated with increased central inflammation affecting neurogenesisrelated cognitive processes

Summary

Introduction

Over the last few decades, inflammation has been identified as one of the main pathophysiological mechanisms underlying psychiatric conditions [1, 2].

Results

Conclusion