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

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.

Associations of Dietary Intake on Biological Markers of Inflammation in Children and Adolescents: A Systematic Review

“…Low-grade inflammation, reflected in the overproduction of acute phase proteins such as C-reactive protein (CRP), pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TFN-α) has been established as a risk factor for several neuropsychiatric disorders [ 3 ], including depression [ 4 , 5 , 6 , 7 ] and schizophrenia [ 8 ]. Moreover, low-grade inflammation in children and adolescents has been associated with the development of co- and multi-morbid conditions to mental health pathologies [ 9 , 10 , 11 , 12 ], including cardiovascular disease [ 13 , 14 ], metabolic syndrome [ 15 ], type-II diabetes [ 16 ] and obesity [ 17 ], therefore making inflammation an important therapeutic target to study, especially for individuals suffering from those conditions.…”

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

“…Based on mounting evidence proving that n- 3-PUFA have beneficial effects on people affected by depression, schizophrenia, and bipolar disorder 115 – 117 in combination with data on the correlation between mTOR and other pathologies (e.g., cancer), Shirooie and colleagues 118 reviewed that mTOR can be one of n -3-PUFA’s targets to treat neurodegenerative diseases by regulating essential cellular processes such as apoptosis and autophagy. In addition, Giacobbe and colleagues 119 have recently discussed the anti-inflammatory effect of n -3-PUFA within the context of neuropsychiatric disorders such as depression. This review mentions that intracerebroventricular injections of resolvins D1, D2, and E1 ( n -3-PUFA metabolites) seem to attenuate depressive-like behavior in mice via activation of mTORC1-signaling pathway 120 , 121 .…”

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

“…[ 95 ]. All these actions confer anti-inflammatory, antithrombotic, lipid-lowering, and vasodilating properties to omega-3 PUFAs [ 96 , 97 , 98 ] that can be exploited for the treatment of human pathologies characterized by a high level of inflammation, including neurodegenerative conditions [ 99 , 100 , 101 ].…”