title: Increased Olfactory Bulb BDNF Expression Does Not Rescue Deficits in Olfactory Neurogenesis in the Huntington's Disease R6/2 Mouse.
abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin protein (mhtt) interferes with the actions of brain-derived neurotrophic factor (BDNF), and BDNF signaling is reduced in the diseased striatum. Loss of this trophic support is thought to contribute to loss of striatal medium spiny neurons in HD. Increasing BDNF in the adult striatum or ventricular ependyma slows disease progression in HD mouse models, and diverts subventricular zone (SVZ)-derived neuroblasts from their normal destination, the olfactory bulb, to the striatum, where some survive and develop features of mature neurons. Most neuroblasts that migrate to the olfactory bulb differentiate as granule cells, with approximately half surviving whereas others undergo apoptosis. In the R6/2 HD mouse model, survival of adult-born granule cells is reduced. Newly maturing cells express the BDNF receptor TrkB, suggesting that mhtt may interfere with normal BDNF trophic activity, increasing their loss. To determine if augmenting BDNF counteracts this, we examined granule cell survival in R6/2 mice that overexpress BDNF in olfactory bulb. Although we detected a decline in apoptosis, increased BDNF was not sufficient to normalize granule cell survival within their normal target in R6/2 mice.
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
authors.forename: Shamayra
authors.initials: S
authors.lastname: Smail
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
authors.forename: Dalbir
authors.initials: D
authors.lastname: Bahga
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
authors.forename: Brittnee
authors.initials: B
authors.lastname: McDole
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA kguthrie@health.fau.edu.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Guthrie
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000378:metabolism / Q000503:physiopathology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012903:Smell; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse
keywords: TrkB; brain-derived neurotrophic factor; granule cells; huntingtin; olfactory bulb; subventricular zone