DX69
The Effect of Glatiramer Acetate Treatment on Mitochondrial Fission/Fusion in EAE
Thursday, May 29, 2014
Trinity Exhibit Hall
Vamshi Nimmagadda, M.B.B.S.
,
Neurology, University of Maryland School of Medicine, Baltimore, MD
Christopher T Bever Jr., M.D., M.B.A.
,
VA MS Center of Excellence - East, VA Maryland Health Care System, Baltimore, MD
Rupal Jain, BA
,
Neurology, University of Maryland School of Medicine, Baltimore, MD
Susan I Judge, Ph.D.
,
VA MS Center of Excellence - East, VA Maryland Health Care System, Baltimore, MD
David Trisler, Ph.D.
,
VA MS Center of Excellence - East, VA Maryland Health Care System, Baltimore, MD
Tapas K Makar, Ph.D.
,
Neurology, University of Maryland School of Medicine, Baltimore, MD
PDF
Background: The approved disease modifying therapies (DMTs) for multiple sclrosis (MS) primarily target inflammation rather than neurodegeneration even though the latter is more closely linked to disability. Some MS DMTs, such as glatiramer acetate (GA), may reduce neurodegeneration in MS, but the mechanism for that effect is not fully understood. Mitochondrial dysfunction appears to play a key role in other neurodegenerative conditions and could play a role in MS. One indicator of mitochondrial stress and dysfunction is changes in mitochondrial fission and fusion.
Objectives: Determine the effect of GA treatment on mitochondrial stress as evidenced by changes in fission and fusion.
Methods: Experimental allergic encephalomyelitis (EAE) was induced in C57Bl/6 female mice by immunization with myelin oligodendroglial glycoprotein peptide 35-55. GA (150 ug/mouse/day) was administered intraperitoneally starting at disease onset. Mice were euthanized on day 20 of GA treatment and brains and spinal cords were examined histologically.
Results: Perivascular cell infiltration and demyelination which was present in the spinal cords of the untreated EAE mice were reduced by GA treatment. Mitochondrial Fis1 (a key regulator of mitochondrial fission) was increased in untreated EAE mice but not in GA treated EAE mice and Mito fusion -2 (a key regulator of fusion) was reduced in untreated EAE mice but not in GA treated EAE mice.
Conclusions: These results suggest a GA mediated increase in mitochondrial fission and reduced fusion which could be due to reduced inflammation resulting in reduced mitochondrial stress.
