Docosahexaenoic acid (22:6n-3) ameliorated the onset and severity of experimental autoimmune encephalomyelitis in mice

Authors: Adkins, Yuriko; SOULIKA, ATHENA - University Of California; Mackey, Bruce; Kelley, Darshan

Submitted to: Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2019
Publication Date: 2/14/2019
Citation: Adkins, Y.C., Soulika, A.M., Mackey, B.E., Kelley, D.S. 2019. Docosahexaenoic acid (22:6n-3) ameliorated the onset and severity of experimental autoimmune encephalomyelitis in mice. Lipids. 54(1):13-23. https://doi.org/10.1002/lipd.12130.
DOI: https://doi.org/10.1002/lipd.12130

Interpretive Summary: A number of central nervous system (CNS) diseases including Alzheimer’s, Parkinson’s, depression, and multiple sclerosis (MS) are associated with increased neuroinflammation and decrease in brain DHA content. Costs associated with brain disorders and mental illness have been rising sharply, and have surpassed all other individual health burdens. Recent intervention studies have demonstrated that DHA supplementation delayed the development of some of the inflammatory diseases of CNS. MS is a neurologic autoimmune disease in which the immune system attacks and degrades the myelin sheaths on axons in brain, spinal cord, and optic nerves, eventually causing irreparable axonal damage and neuronal death. It is the leading cause of non-traumatic neurologic disability in young adults in US and Europe. Studies comparing krill and fish oils suggest that krill oil may be more efficient than fish oil in the tissue accretion of long chain n-3 PUFA. This difference in the accretion of the n-3 PUFA is believed to result from the structure of the lipids that contain these fatty acids; krill oil contains 40-50% n-3 PUFA in the phospholipid (PL) form, while fish oil is primarily the triglyceride (TG) form with less than 0.5% in PL form. In this study we compared the effects of PL-DHA and TG-DHA on the onset and severity of experimental autoimmune encephalitis (EAE) in a mouse model of MS. Female mice were fed a low n-3 PUFA diet (control) for 2 weeks and then fed 5 experimental diets (control, 0.3 and 1.0% each of PL- and TAG-DHA, n=12/group) for next 8 weeks. EAE was induced by injecting myelin oligodendrocyte glycoprotein 4 weeks after the start of experimental diets and the onset and severity of EAE was monitored every day for the next 28 days. Onset of the disease was delayed in all DHA groups compared with the control group and the EAE score at the end of study was inversely associated with the brain concentration of DHA. This inverse association indicates that DHA decreased progression of disease and/or enhanced recovery from it. During the onset phase of disease (d 9-16 after induction) the EAE score pooled for all DHA groups was significantly lower than that in the control group. For the progression phase (d 17-22), EAE score trended lower in 0.3% TAG-DHA and for recovery phase (d 23-28), 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, but in the final outcome, PL-DHA may be more effective than TAG-DHA. Further studies with greater number of animals and longer duration of disease are needed to confirm these differences between the effects of the two forms of DHA.

Technical Abstract: Multiple sclerosis (MS) is a neurologic autoimmune disease which is the leading cause of non-traumatic neurologic disability in young adults in US and Europe. N-3 PUFA have been reported to mitigate severity of this disease. Recent studies suggest that phospholipids (PL) form of dietary n-3 PUFA may lead to their higher tissue accretion than triglyceride (TAG) form. We compared efficacy of the PL- and TAG-DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low ALA diet (control) for 2 weeks and then fed either control or 0.3, 1.0%, PL- or TAG-DHA diets (n=12/group) for 4 weeks pre- and 4 weeks post-induction of EAE. Onset of disease was delayed by both forms and concentrations of DHA, and the inverse association between EAE score brain DHA concentration was not significant at the end of study (P=0.08). Daily EAE scores did not differ between each DHA group from control group, however, during the onset phase (d 9-16 after induction), scores in the DHA groups collectively were significantly (P=0.028) lower than in the control group. During progression phase (d 17-22), EAE score trended lower in 0.3% TAG-DHA and during recovery phase (d 23-28), 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, but in the final outcome, PL-DHA may be more effective than TAG-DHA. Further studies are needed to confirm these differences.