title: Changes in expression of vascular endothelial growth factor and its receptors in the aging mouse cochlea, part 1: the normal-hearing mouse.
abstract: BACKGROUND
  Presbycusis is the most common degenerative otologic condition. New research is pointing toward vascular changes within the cochlea with age. Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and Flk-1, are important regulators of angiogenesis.
  
  
  OBJECTIVE
  The aim of this study was to characterize the hearing, VEGF expression, and vasculature of young and old Swiss Webster (SW) mice.
  
  
  METHODS
  Young (4 weeks, n = 14) and aged (32-36 weeks; n = 14) SW mice were used. Hearing was evaluated using the auditory brainstem response. Changes in VEGF, Flt-1, and Flk-1 expression and histology were evaluated by immunohistochemistry and real-time polymerase chain reaction (quantitative PCR).
  
  
  RESULTS
  Aged SW mice demonstrated clinically stable hearing with age with mean hearing thresholds dropping 5.7, 4.2, 6.5, and 10.9 dB peSPL with age at 4, 8, 16, and 32 kHz pure-tone stimuli, respectively. Immunohistochemistry showed the presence of VEGF, Flt-1, and Flk-1 in the stria vascularis, spiral ganglion, and organ of Corti. Strong expression was found within the hair cells and the stria vascularis. Immunohistochemistry and qPCR demonstrated no difference in expression levels between age groups or between apical and basal turns of the cochlea. Microscopy demonstrated no difference in the number or density of stria vascularis vessels between age groups.
  
  
  CONCLUSIONS
  We describe a mouse model of stable hearing with aging. Stria vascularis vasculature and expression of VEGF, Flt-1, and Flk-1 do not change with age, and there appears to be no apical to basal differential expression. These results provide valuable normalized data to compare VEGF expression and vasculature patterns to other mouse strains.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON.
authors.forename: Thileeban
authors.initials: T
authors.lastname: Kandasamy
authors.forename: David J
authors.initials: DJ
authors.lastname: Clinkard
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Stephen
authors.initials: S
authors.lastname: Chen
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Chen
authors.forename: Robert V
authors.initials: RV
authors.lastname: Harrison
authors.forename: Vincent Y W
authors.initials: VY
authors.lastname: Lin
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003051:Cochlea / Q000098:blood supply / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006309:Hearing / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2