title: TrkB agonist, 7,8-dihydroxyflavone, reduces the clinical and pathological severity of a murine model of multiple sclerosis.
abstract: 7,8-Dihydroxyflavone (DHF), is a recently described TrkB agonist that readily crosses the blood brain barrier. We treated C57Bl/6 mice with MOG--induced EAE daily with DHF starting on the day of disease induction. Clinical severity of impairment was reduced throughout the course of disease. Pathological examination of brains and spinal cords on day 28 showed that DHF treatment increased the phosphorylation of TrkB and activated downstream signaling pathways including AKT and STAT3 and reduced inflammation, demyelination and axonal loss compared to EAE controls. DHF treatment duplicated the central nervous system effects of brain derived neurotrophic factor in the EAE.
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, United States. Electronic address: tmakar@som.umaryland.edu.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Makar
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States. Electronic address: vnimmagadda@som.umaryland.edu.
authors.forename: Vamshi K C
authors.initials: VK
authors.lastname: Nimmagadda
authors.affiliation: Research Service, VA Medical Center, Baltimore, MD 21201, United States; Department of Medicine, University of Maryland, Baltimore, MD 21201, United States. Electronic address: isingh@umaryland.edu.
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Singh
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States. Electronic address: knl2fv@virginia.edu.
authors.forename: Kristal
authors.initials: K
authors.lastname: Lam
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States. Electronic address: fahadm1@umbc.edu.
authors.forename: Fahad
authors.initials: F
authors.lastname: Mubariz
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, United States. Electronic address: sjudge@som.umaryland.edu.
authors.forename: Susan I V
authors.initials: SI
authors.lastname: Judge
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, United States. Electronic address: GTrisler@som.umaryland.edu.
authors.forename: David
authors.initials: D
authors.lastname: Trisler
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, United States. Electronic address: christopher.bever@va.gov.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Bever
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D005260:Female; D047309:Flavones / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy*; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C485383:6,7-dihydroxyflavone; D016207:Cytokines; D047309:Flavones; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D051028:bcl-2-Associated X Protein; C445081:myelin oligodendrocyte glycoprotein (35-55); D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases
keywords: Central nervous system; Demyelination; Experimental autoimmune encephalomyelitis; Inflammation; Neuroprotection; Remyelination; TrkB Signal Transduction