Role of omega-3 endocannabinoids in the modulation of T-cell activity in a multiple sclerosis experimental autoimmune encephalomyelitis (EAE) model

Kim, Justin S.; Soto-Diaz, Katiria; Bingham, Tanner W.; Steelman, Andrew J.; Das, Aditi

doi:10.1016/j.jbc.2023.102886

Cited by 4 publications

(4 citation statements)

References 82 publications

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“…18 ALA can be converted to two somewhat longer n-3 PUFAs, eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), which are both physiologically significant, 18 and whose ethanolamine derivatives (DHEA, EPEA) are recognized as ω-3 endocannabinoids. 19 The mammalian brain contains large amounts of fatty acids, of which 50% are PUFAs. 20 AA and DHA are particularly efficacious to alter the biophysical properties of cell membranes, transporters, and receptors, thus modulating neurotransmitter action ubiquitously in neural networks.…”

Section: Pufas: Biochemistry In a Nutshellmentioning

confidence: 99%

“…We illustrate this by the finding that the effect of EPA on NSC proliferation can be abolished by prior exposure of NSCs to antagonists of either the CB 1 R or CB 2 cannabinoid receptor (CB 2 R). 90,127 molecules (designated as "n-3 endocannabinoid" 19 ), including a shared biosynthetic mechanism with arachidonoylethanolamine. 69,140 DHEA induces neuronal differentiation (neuritogenesis, synaptogenesis) 138 by activating protein kinase A (PKA)/cAMP response element binding (CREB) signaling through GPR110.…”

Section: ω-3 Pufasmentioning

confidence: 99%

“…LA can be converted into arachidonic acid (AA; 20:4 n‐6), which then serves as a precursor to n‐6 endocannabinoids/endovanilloids, prostaglandins, thromboxane, and leukotrienes, as well as their derivatives 18 . ALA can be converted to two somewhat longer n‐3 PUFAs, eicosapentaenoic acid (EPA; 20:5 n‐3) and docosahexaenoic acid (DHA; 22:6 n‐3), which are both physiologically significant, 18 and whose ethanolamine derivatives (DHEA, EPEA) are recognized as ω‐3 endocannabinoids 19 …”

Section: Pufas: Biochemistry In a Nutshellmentioning

confidence: 99%

“…Here, a crosstalk between DHA and endocannabinoid‐mediated signaling pathways could be suggested by DHA being converted, at least in part, into N‐docosahexaenoylethanolamide (DHEA). DHEA belongs to the N ‐acetylated amino acid or neurotransmitter class of lipid signaling molecules (designated as “n‐3 endocannabinoid” 19 ), including a shared biosynthetic mechanism with arachidonoylethanolamine 69,140 . DHEA induces neuronal differentiation (neuritogenesis, synaptogenesis) 138 by activating protein kinase A (PKA)/cAMP response element binding (CREB) signaling through GPR110 141 .…”

Section: Mechanistic Insights In Pufa Action On Neuronal Developmentmentioning

confidence: 99%

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Adverse effects of gestational ω‐3 and ω‐6 polyunsaturated fatty acid imbalance on the programming of fetal brain development

Cinquina

Keimpema

Pollak

et al. 2023

J Neuroendocrinology

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Obesity is a key medical challenge of our time. The increasing number of children born to overweight or obese women is alarming. During pregnancy, the circulation of the mother and her fetus interact to maintain the uninterrupted availability of essential nutrients for fetal organ development. In doing so, the mother's dietary preference determines the amount and composition of nutrients reaching the fetus. In particular, the availability of polyunsaturated fatty acids (PUFAs), chiefly their ω‐3 and ω‐6 subclasses, can change when pregnant women choose a specific diet. Here, we provide a succinct overview of PUFA biochemistry, including exchange routes between ω‐3 and ω‐6 PUFAs, the phenotypes, and probable neurodevelopmental disease associations of offspring born to mothers consuming specific PUFAs, and their mechanistic study in experimental models to typify signaling pathways, transcriptional, and epigenetic mechanisms by which PUFAs can imprint long‐lasting modifications to brain structure and function. We emphasize that the ratio, rather than the amount of individual ω‐3 or ω‐6 PUFAs, might underpin physiologically correct cellular differentiation programs, be these for neurons or glia, during pregnancy. Thereupon, the PUFA‐driven programming of the brain is contextualized for childhood obesity, metabolic, and endocrine illnesses.

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Section: Pufas: Biochemistry In a Nutshellmentioning

confidence: 99%

Section: ω-3 Pufasmentioning

confidence: 99%

Section: Pufas: Biochemistry In a Nutshellmentioning

confidence: 99%

Section: Mechanistic Insights In Pufa Action On Neuronal Developmentmentioning

confidence: 99%

See 2 more Smart Citations

Adverse effects of gestational ω‐3 and ω‐6 polyunsaturated fatty acid imbalance on the programming of fetal brain development

Cinquina

Keimpema

Pollak

et al. 2023

J Neuroendocrinology

View full text Add to dashboard Cite

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Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis

Muñoz-Jurado,

Escribano,

Galván

et al. 2024

The Journal of Nutritional Biochemistry

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“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Schmidt,

Hébert,

Wallukat

et al. 2023

Children

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Background: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer–BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year. Conclusions: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.

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Role of omega-3 endocannabinoids in the modulation of T-cell activity in a multiple sclerosis experimental autoimmune encephalomyelitis (EAE) model

Cited by 4 publications

References 82 publications

Adverse effects of gestational ω‐3 and ω‐6 polyunsaturated fatty acid imbalance on the programming of fetal brain development

Adverse effects of gestational ω‐3 and ω‐6 polyunsaturated fatty acid imbalance on the programming of fetal brain development

Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis

“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

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