Neurotrophin 3, not brain-derived neurotrophic factor or neurotrophin 4, knockout mice have delay in vestibular compensation after unilateral labyrinthectomy.
On the basis that neurotrophins (NTs) affect neuronal synaptic plasticity, are expressed in various cell types of the vestibular system, and exert a trophic influence on statoacoustic neurons, the authors hypothesized a role for NTs in vestibular compensation. To test this hypothesis, they performed unilateral surgical labyrinthectomy in 11 heterozygous (+/-) neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF) knockout mice and in two neurotrophin 4 (NT4) homozygous (-/-) knockout mice, each with a control (+/+) sibling, for a total of 26 mice. Four BDNF(+/-) and four NT3(+/-) mice with their (+/+) controls each were allowed to recover in a normal lighted room for 3, 7, 14, and 30 days following labyrinthectomy. Two BDNF(+/-) and two NT4(-/-) mice with controls were kept in total darkness for 1- and 16-day survival periods. One NT3(+/-) mouse without a control (which died in surgery) was sacrificed after 16 days in darkness. The behavior of all mice was videorecorded to monitor their recovery. Compared with normal (+/+) littermate controls, NT3(+/-) mice demonstrated a delay in compensation (8 to 10 days) in light surround, whereas NT4(-/-) mice showed only a minor delay in dark surround. Despite a 40% lower vestibular ganglion cell population in BDNF(+/-) mice compared with (+/+) controls, BDNF(+/-) mice did not reveal a detectable delay in recovery following labyrinthectomy. These findings suggest that a 50% loss of NT3 protein significantly affects vestibular recovery in adult mice. Perhaps variations in achieving vestibular compensation in humans may be partly secondary to genetically different NT3 levels in vestibular pathways.
Gacek
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Department of Otolaryngology and Communication Sciences, State University of New York Health Science Center, Syracuse, USA.
Khetarpal
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D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D007758:Ear, Inner / Q000601:surgery*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D020933:Neurotrophin 3; D014722:Vestibule, Labyrinth / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C073922:neurotrophin 4