Changes in expression of vascular endothelial growth factor and its receptors in the aging mouse cochlea, part 1: the normal-hearing mouse

J Otolaryngol Head Neck Surg. 2012 Apr;41 Suppl 1:S36-42.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Cochlea / blood supply
  • Cochlea / physiology*
  • Gene Expression Regulation, Developmental*
  • Hearing / physiology*
  • Immunohistochemistry
  • Mice
  • Neovascularization, Physiologic / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2