Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection

Trépanier, Marc-Olivier; Hopperton, Kathryn E.; Giuliano, Vanessa; Masoodi, Mojgan; Bazinet, Richard P.

doi:10.1016/j.neuint.2018.05.010

Cited by 6 publications

(11 citation statements)

References 70 publications

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“…Hashimoto et al found the same in the cortex of aged rats (Hashimoto et al, 2015). These results differ from those of Trépanier et al who found that, in a model of Fat-1 mice, a greater increase in brain DHA induced by dietary supply has no effect on the resolution of inflammation after an icv LPS injection (Trépanier et al, 2018).…”

Section: Regulation Of the N-3 Pufa-derived Spmscontrasting

confidence: 99%

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

2019

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In the past few decades, as a result of their anti-inflammatory properties, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), have gained greater importance in the regulation of inflammation, especially in the central nervous system (in this case known as neuroinflammation). If sustained, neuroinflammation is a common denominator of neurological disorders, including Alzheimer’s disease and major depression, and of aging. Hence, limiting neuroinflammation is a real strategy for neuroinflammatory disease therapy and treatment. Recent data show that n-3 LC-PUFAs exert anti-inflammatory properties in part through the synthesis of specialized pro-resolving mediators (SPMs) such as resolvins, maresins and protectins. These SPMs are crucially involved in the resolution of inflammation. They could be good candidates to resolve brain inflammation and to contribute to neuroprotective functions and could lead to novel therapeutics for brain inflammatory diseases. This review presents an overview 1) of brain n-3 LC-PUFAs as precursors of SPMs with an emphasis on the effect of n-3 PUFAs on neuroinflammation, 2) of the formation and action of SPMs in the brain and their biological roles, and the possible regulation of their synthesis by environmental factors such as inflammation and nutrition and, in particular, PUFA consumption.

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Section: Regulation Of the N-3 Pufa-derived Spmscontrasting

confidence: 99%

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

2019

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“…Recently, the i.c.v. injection of LPS to mice with increased DHA content, due to dietary fish oil supplementation or fat-1 transgene expression, revealed little to no protective role for DHA in the neuroinflammatory response to LPS (30). In agreement with these results, our data show that the neuroinflammatory response to LPS was not augmented in male Acsl6-mediated DHA deficiency.…”

Section: Discussionsupporting

confidence: 88%

“…Together these data show impaired neurosensory and motor function in Acsl6 −/− mice. DHA has been shown to attenuate neuroinflammation in response to lipopolysaccharide (LPS) exposure in some, but not all, reports (27)(28)(29)(30)(31). To determine if Acsl6-mediated DHA deficiency altered neuroinflammation in the brain and in response to LPS, control and Acsl6 −/− male mice were given a single i.p.…”

Section: Resultsmentioning

confidence: 99%

“…DHA has received recent attention for its antiinflammatory properties (9)(10)(11)(38)(39)(40). However, not all reports are consistent with reduced neuroinflammation by DHA (27)(28)(29)(30)(31)(41)(42)(43). Because dietary DHA manipulation involves whole-body metabolism of DHA, the neuroprotective effects could be elicited by responses outside the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

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Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain

Fernandez

Kim

Zhao

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly abundant in the brain and confers protection against numerous neurological diseases, yet the fundamental mechanisms regulating the enrichment of DHA in the brain remain unknown. Here, we have discovered that a member of the long-chain acyl-CoA synthetase family, Acsl6, is required for the enrichment of DHA in the brain by generating an Acsl6-deficient mouse (Acsl6 −/− ). Acsl6 is highly enriched in the brain and lipid profiling of Acsl6 −/− tissues reveals consistent reductions in DHA-containing lipids in tissues highly abundant with Acsl6. Acsl6 −/− mice demonstrate motor impairments, altered glutamate metabolism, and increased astrogliosis and microglia activation. In response to a neuroinflammatory lipopolysaccharide injection, Acsl6 −/− brains show similar increases in molecular and pathological indices of astrogliosis compared with controls. These data demonstrate that Acsl6 is a key mediator of neuroprotective DHA enrichment in the brain. fatty acid metabolism | neurometabolism | docosahexaenoic acid | acyl-CoA synthetase | brain lipids

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“…Similarly, Hopperton et al reported no detectable concentrations of the SPMs protectin, maresin or resolvins (D and E series) in Fat-1 mouse model of Alzheimer’s disease (AD), and these concentrations remained undetectable over 12 weeks, despite consumption of a diet containing 2.4% EPA and 1.1% of DHA [38]. Trépanier et al [39] also noted a general absence of SPMs following direct intracerebral ventricular injection of LPS (a bacterial metabolite which stimulates a measureable inflammatory response) in a murine model over 28 days, causing the authors to conclude that the resolution of brain inflammation was mediated independently of SPMs.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

et al. 2019

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Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease).

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Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection

Cited by 6 publications

References 70 publications

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

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