Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants

Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark; Tojo, Luis M.; Cannazza, Giuseppe; Su, Kuan‐Pin; Pariante, Carmine M.; Zunszain, Patricia A.

doi:10.1016/j.bbi.2017.05.006

Cited by 108 publications

(113 citation statements)

References 78 publications

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“…Monoaminergic antidepressants and also omega-3 fatty acids were demonstrated to reduce neurotoxic effects related to Trp breakdown (246). Omega-3 fatty acids contribute to the beneficial effects of the Mediterranean diet, which is regarded as anti-inflammatory diet (247).…”

Section: Nutrition Microbiome and Physical Activity And Its Associamentioning

confidence: 99%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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Section: Nutrition Microbiome and Physical Activity And Its Associamentioning

confidence: 99%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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“…The effects of DHA on different brain cell populations has been most extensively studied in the rat hippocampus. Several studies have investigated the effects of DHA on hippocampal progenitor populations and hippocampal function and found that it promotes neuronal differentiation and survival through a number of mechanisms including increasing retinoid-X receptor and pro-neuronal bHLH gene expression (Calderon and Kim, 2007;Katakura, et al, 2009;Kim et al 2000;Dyall et al, 2010), it promotes progenitor proliferation in disease models (da Costa, et al, 2010;Borsini et al, 2017;Fiol-deRoque, et al, 2013), and it has a functional impact on learning and memory (Lozada et al, 2017;He et al, 2009). Our observations of SVZ cells have found the effects of DHA treatment on progenitor populations may differ significantly from the SGZ, such as a lack of a direct effect on the proliferation rate.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

Belle

Sperry

Ludwig

et al. 2020

Preprint

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Fatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair. Significance StatementWe have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.

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“…Besides IL-1 β , other inflammatory markers have also been noted to be involved in the pathogenesis of depression such as tumor necrosis factor- α (TNF- α ) and interferon- γ (IFN- γ ) [52]. Fish oils are relevant to this discussion because one study demonstrated that EPA and DHA, along with sertraline (SSRI) and venlafaxine (SNRI), were able to reverse the effects of IL-1 β at human hippocampal cells in vitro [4]. Similar findings have also been shown in clinical trials using patients treated with IFN- α to combat hepatitis C infections.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Fish oil and depression: The skinny on fats

Burhani

Rasenick

2017

JIN

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Depression is the leading cause of disability worldwide, and even though many forms of therapy exist, about one third of patients treated with conventional antidepressants do not experience a response. For these reasons, new approaches to treat depression, including fish oil, are being investigated. Fish oil is known to have many beneficial side effects, and clinical trials demonstrate that supplementation with fish oil is beneficial in the management of depression. Fish oil contains omega-3 polyunsaturated fatty acids (PUFA), and there are several mechanisms by which PUFAs are thought to induce an antidepressant effect, including anti-inflammatory action and direct effects on membrane properties. This review will analyze and evaluate the clinical trials surrounding fish oil use in the treatment of depression, and will also review the likely sites of action of PUFAs at the cell membrane with special attention being placed on lipid rafts and G-proteins.

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Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants

Cited by 108 publications

References 78 publications

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

Fish oil and depression: The skinny on fats

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