title: 7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is an enigmatic neurodegenerative disorder without any effective treatment characterized by loss of motor neurons (MNs) that results in rapidly progressive motor weakness and early death due to respiratory failure. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family known to play a prominent role in the differentiation and survival of MNs. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) is a potent and selective small molecule tyrosine kinase receptor B (TrkB) agonist that mimics the effects of BDNF. In the present study, we evaluated the neuroprotective effects of 7,8-DHF in a transgenic ALS mouse model (SOD1(G93A)). We found that chronic administration of 7,8-DHF significantly improved motor deficits, and preserved spinal MNs count and dendritic spines in SOD1(G93A) mice. These data suggest that 7,8-DHF should be considered as a potential therapy for ALS and the other motor neuron diseases.
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA; Physiology and Neurophysiology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir 26480, Turkey.
authors.forename: Orhan Tansel
authors.initials: OT
authors.lastname: Korkmaz
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Nurgul
authors.initials: N
authors.lastname: Aytan
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Carreras
authors.affiliation: Radiology, MGH and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ji-Kyung
authors.initials: JK
authors.lastname: Choi
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.affiliation: Radiology, MGH and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Jenkins
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Radiology, MGH and Harvard Medical School, Boston, MA 02114, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dedeoglu@bu.edu.
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Dedeoglu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009048:Motor Skills / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020813:Receptor, trkB / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C478869:7,8-dihydroxyflavanone; D044950:Flavanones; D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020813:Receptor, trkB
keywords: 7,8-Dihydroxyflavone; Amyotrophic lateral sclerosis; BDNF; Motor neurons; TrkB