Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke

Yamagata, Kazuo

doi:10.1002/jnr.24728

Cited by 16 publications

(10 citation statements)

References 88 publications

(134 reference statements)

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“…The antioxidant properties of DHA and its metabolites, resolvins, neuroprotectins and 4-hydroxy-2E-hexenal, are mediated by Nrf2 activation and involve upregulation of heme oxygenase 1 (HO-1) to protect the brain against ischemic damage [ [78] , [79] , [80] ]. Post-stroke administration of DHA is effective in reducing brain injury [ [81] , [82] , [83] ] and improving sensorimotor function [ 84 , 85 ]. Notably, stroke lowers blood SCFA concentrations, and SCFA supplementation has been reported to reduce damage following post-stroke reperfusion [ [86] , [87] , [88] , [89] ].…”

Section: Protective Role Of Scfas Against Oxidative and Mitochondrial Stress Involving Keap1-nrf2 Signalingmentioning

confidence: 99%

Short-chain fatty acids as modulators of redox signaling in health and disease

et al. 2021

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Short-chain fatty acids (SCFAs), produced by colonic bacteria and obtained from the diet, have been linked to beneficial effects on human health associated with their metabolic and signaling properties. Their physiological functions are related to their aliphatic tail length and dependent on the activation of specific membrane receptors. In this review, we focus on the mechanisms underlying SCFAs mediated protection against oxidative and mitochondrial stress and their role in regulating metabolic pathways in specific tissues. We critically evaluate the evidence for their cytoprotective roles in suppressing inflammation and carcinogenesis and the consequences of aging. The ability of these natural compounds to induce signaling pathways, involving nuclear erythroid 2-related factor 2 (Nrf2), contributes to the maintenance of redox homeostasis under physiological conditions. SCFAs may thus serve as nutritional and therapeutic agents in healthy aging and in vascular and other diseases such as diabetes, neuropathologies and cancer.

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Section: Protective Role Of Scfas Against Oxidative and Mitochondrial Stress Involving Keap1-nrf2 Signalingmentioning

confidence: 99%

Short-chain fatty acids as modulators of redox signaling in health and disease

et al. 2021

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“…Further, DHA and NPD1 have been shown to modulate apoptotic induction in different models of neurodegeneration (reviewed in [4,40,[47][48][49][50][51]). For instance, exposure to oxidative challenge, intraventricular infusion of Aβ peptides, induction of excitotoxicity or ischemia/reperfusion maneuvers all appear to share a common pattern of enhancement of pro-apoptotic proteins Bik and Bax, which is totally or partially counteracted by treatments with DHA or NPD1 [4,41,[49][50][51][52]. On the other hand, anti-apoptotic proteins Bcl-2, Bcl-xl and Bfl-1 were enhanced by DHA and docosahexaenoic-acid-derived mediators, including the recently discovered very-long-chain DHA-derived mediators elovanoids, such as ELV-N32 and ELV-N34 [47].…”

Section: Dha Is a Pleiotropic Molecule In Nerve Cellsmentioning

confidence: 99%

DHA and Its Elaborated Modulation of Antioxidant Defenses of the Brain: Implications in Aging and AD Neurodegeneration

2021

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DHA (docosahexaenoic acid) is perhaps the most pleiotropic molecule in nerve cell biology. This long-chain highly unsaturated fatty acid has evolved to accomplish essential functions ranging from structural components allowing fast events in nerve cell membrane physiology to regulation of neurogenesis and synaptic function. Strikingly, the plethora of DHA effects has to take place within the hostile pro-oxidant environment of the brain parenchyma, which might suggest a molecular suicide. In order to circumvent this paradox, different molecular strategies have evolved during the evolution of brain cells to preserve DHA and to minimize the deleterious effects of its oxidation. In this context, DHA has emerged as a member of the “indirect antioxidants” family, the redox effects of which are not due to direct redox interactions with reactive species, but to modulation of gene expression within thioredoxin and glutathione antioxidant systems and related pathways. Weakening or deregulation of these self-protecting defenses orchestrated by DHA is associated with normal aging but also, more worryingly, with the development of neurodegenerative diseases. In the present review, we elaborate on the essential functions of DHA in the brain, including its role as indirect antioxidant, the selenium connection for proper antioxidant function and their changes during normal aging and in Alzheimer’s disease.

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“…In addition, NPD1 remains one of our most prominently detected mediators increased by LPS in our sCVOs cultures. This small pro-resolving lipid mediator (SPM) has multiple beneficial effects during brain inflammatory insults such as ischemic or traumatic brain injury [ 88 ] via preservation of mitochondrial membrane structure [ 89 ] or blockage of neuronal apoptosis and antioxidative effects [ 90 ]. However, caution needs to be taken as this mediator is hard to distinguish from its isomer protectin DX [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

Pflieger

Wolf

Feldotto

et al. 2022

IJMS

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Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood–brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)α bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNFα levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNFα levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication.

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Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke

Cited by 16 publications

References 88 publications

Short-chain fatty acids as modulators of redox signaling in health and disease

Short-chain fatty acids as modulators of redox signaling in health and disease

DHA and Its Elaborated Modulation of Antioxidant Defenses of the Brain: Implications in Aging and AD Neurodegeneration

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

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