Docosahexaenoic acid (22:6n-3) Ameliorated the Onset and Severity of Experimental Autoimmune Encephalomyelitis in Mice

Yuriko Adkins, Athena Soulika, Bruce Mackey, Darshan S. Kelley

Research output: Contribution to journalArticle

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Abstract

Multiple sclerosis (MS) is a neurologic autoimmune disease, which is the leading cause of nontraumatic neurologic disability in young adults in United States and Europe. n-3 polyunsaturated fatty acids (PUFA) are reported to mitigate severity of this disease. Recent studies suggest that phospholipid (PL) form of dietary n-3 PUFA may lead to their higher tissue accretion than triacylglycerol (TAG) form. We compared efficacy of PL-docosahexaenoic acid (22:6n-3) (DHA) and TAG-DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low alpha-linolenic acid (18:3n-3) (ALA) diet (control) for 2 weeks and then fed either control, 0.3%, or 1.0% DHA (PL or TAG) for 4 weeks pre-EAE induction and 4 weeks post-EAE induction. The brain and spinal cord n-6:n-3 ratio was significantly lower in all mice fed DHA compared to control. EAE onset was delayed in mice fed both DHA forms and concentrations, except for 1% TAG-DHA. The inverse association between the EAE score and the brain DHA concentration was nonsignificant at the end of the study (p = 0.08). Daily EAE scores of mice fed different DHA diets did not differ from control, however, the score of all DHA groups combined during days 9–16 was lower (p = 0.028) compared to the control. During days 17–22, the EAE score trended lower in 0.3% TAG-DHA and during days 23–28, the EAE score trended lower in both PL-DHA groups than those in all other groups. These findings suggest that TAG-DHA may be more effective than PL-DHA in the early phases of EAE, and in the final outcome, PL-DHA may be more effective than TAG-DHA.

Original languageEnglish (US)
JournalLipids
DOIs
StatePublished - Jan 1 2019

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Autoimmune Experimental Encephalomyelitis
Docosahexaenoic Acids
Triglycerides
Phospholipids
Omega-3 Fatty Acids
Nutrition
Brain
Multiple Sclerosis
Autoimmune Diseases of the Nervous System
alpha-Linolenic Acid
Diet
Nervous System
Tissue
Young Adult
Spinal Cord

Keywords

  • Brain
  • DHA
  • EAE
  • Multiple sclerosis
  • n-3 PUFA
  • n-6 PUFA
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

Docosahexaenoic acid (22:6n-3) Ameliorated the Onset and Severity of Experimental Autoimmune Encephalomyelitis in Mice. / Adkins, Yuriko; Soulika, Athena; Mackey, Bruce; Kelley, Darshan S.

In: Lipids, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Docosahexaenoic acid (22:6n-3) Ameliorated the Onset and Severity of Experimental Autoimmune Encephalomyelitis in Mice",
abstract = "Multiple sclerosis (MS) is a neurologic autoimmune disease, which is the leading cause of nontraumatic neurologic disability in young adults in United States and Europe. n-3 polyunsaturated fatty acids (PUFA) are reported to mitigate severity of this disease. Recent studies suggest that phospholipid (PL) form of dietary n-3 PUFA may lead to their higher tissue accretion than triacylglycerol (TAG) form. We compared efficacy of PL-docosahexaenoic acid (22:6n-3) (DHA) and TAG-DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low alpha-linolenic acid (18:3n-3) (ALA) diet (control) for 2 weeks and then fed either control, 0.3{\%}, or 1.0{\%} DHA (PL or TAG) for 4 weeks pre-EAE induction and 4 weeks post-EAE induction. The brain and spinal cord n-6:n-3 ratio was significantly lower in all mice fed DHA compared to control. EAE onset was delayed in mice fed both DHA forms and concentrations, except for 1{\%} TAG-DHA. The inverse association between the EAE score and the brain DHA concentration was nonsignificant at the end of the study (p = 0.08). Daily EAE scores of mice fed different DHA diets did not differ from control, however, the score of all DHA groups combined during days 9–16 was lower (p = 0.028) compared to the control. During days 17–22, the EAE score trended lower in 0.3{\%} TAG-DHA and during days 23–28, the EAE score trended lower in both PL-DHA groups than those in all other groups. These findings suggest that TAG-DHA may be more effective than PL-DHA in the early phases of EAE, and in the final outcome, PL-DHA may be more effective than TAG-DHA.",
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AB - Multiple sclerosis (MS) is a neurologic autoimmune disease, which is the leading cause of nontraumatic neurologic disability in young adults in United States and Europe. n-3 polyunsaturated fatty acids (PUFA) are reported to mitigate severity of this disease. Recent studies suggest that phospholipid (PL) form of dietary n-3 PUFA may lead to their higher tissue accretion than triacylglycerol (TAG) form. We compared efficacy of PL-docosahexaenoic acid (22:6n-3) (DHA) and TAG-DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low alpha-linolenic acid (18:3n-3) (ALA) diet (control) for 2 weeks and then fed either control, 0.3%, or 1.0% DHA (PL or TAG) for 4 weeks pre-EAE induction and 4 weeks post-EAE induction. The brain and spinal cord n-6:n-3 ratio was significantly lower in all mice fed DHA compared to control. EAE onset was delayed in mice fed both DHA forms and concentrations, except for 1% TAG-DHA. The inverse association between the EAE score and the brain DHA concentration was nonsignificant at the end of the study (p = 0.08). Daily EAE scores of mice fed different DHA diets did not differ from control, however, the score of all DHA groups combined during days 9–16 was lower (p = 0.028) compared to the control. During days 17–22, the EAE score trended lower in 0.3% TAG-DHA and during days 23–28, the EAE score trended lower in both PL-DHA groups than those in all other groups. These findings suggest that TAG-DHA may be more effective than PL-DHA in the early phases of EAE, and in the final outcome, PL-DHA may be more effective than TAG-DHA.

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