N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update

Trépanier, Marc-Olivier; Hopperton, Kathryn E.; Orr, Sarah; Bazinet, Richard P.

doi:10.1016/j.ejphar.2015.05.045

Cited by 94 publications

(61 citation statements)

References 133 publications

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“…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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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“…In fact, recent studies showed that DHA supplementation could prevent neuronal apoptosis via decreasing caspase-3 and Bax expressions [23]. Also DHA had potent effects against neuroinflammation in various models [24, 25]. Whether DHA ameliorated sevoflurane-induced synaptogenesis through inhibiting neuroapoptosis and neuroinflammation was an interesting question and also needed to be elucidated in future.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

Tao

Luo

Xue

et al. 2016

BioMed Research International

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Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.

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“…DHA has a significant role in the reduction of dementia risk (Schaefer et al, 2006). Neuroinflammation can be dampened by DHA supplementation in the pathogenesis of Alzheimer's disease (Kinney et al, 2018; Trépanier et al, 2016). DHA derived anti‐inflammatory eicosanoids, neuroprotectins prevent Alzheimer's disease pathogenesis (Lukiw et al, 2005).…”

Section: Roles Of Dha and Its Metabolites In Brain Functionmentioning

confidence: 99%

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Mallick

Basak

Duttaroy

2019

Intl J of Devlp Neuroscience

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Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca 2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.

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N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update

Cited by 94 publications

References 133 publications

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

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

Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

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