Abstract
Otoconia-related vertigo and balance deficits, particularly benign paroxysmal positional vertigo (BPPV), are common. Our recent studies in humans show that, while BPPV prevalence greatly increases with age in both genders, peri-menopausal women are especially susceptible. In the present study, we show that bilateral ovariectomized (OVX) mice have significant balance behavioral deficits, and that estrogen deficiency compromises otoconia maintenance and anchoring by reducing the expression of otoconial component and anchoring proteins. There is ectopic debris formation in the ampulla under estrogen deficiency due to aberrant matrix protein expression. Furthermore, phytoestrogen is effective in rescuing the otoconia abnormalities. By comparing the expression levels of known estrogen receptor (Esr) subtypes, and by examining the otoconia phenotypes of null mice for selected receptors, we postulate that Esr2 may be critical in mediating the effects of estrogen in otoconia maintenance.
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Researchers from the University of Southern California and Harvard discovered a novel way for a drug to zero in on damaged nerves and cells inside the ear, a remedy that could potentially restore the hearing of those who suffer from sensorineural hearing loss. (Bioconjug Chem. 2018;29[4]:1240.) They designed and tested a bisphosphonate conjugate of 7,8-Dihydroxyflavone (Ris-DHF), a known, potent agonist of the tropomyosin receptor kinase B that protects the cochlear spiral ganglion neurons (SGNs) from apoptosis. They found that Ris-DHF increases neurite outgrowth in vitro, maintains this ability after binding to hydroxyapatite, and regenerates synapses in kainic acid-damaged cochlear organ of Corti explants dissected in vitro with attached SGNs. Charles E. McKenna, a corresponding author for the study and chemistry professor at the USC Dornsife College of Letters, Arts and Sciences, said what's new here is they figured out how to deliver a drug into the inner ear so it actually stays put. "Inside this part of the ear, there's fluid constantly flowing that would sweep dissolved drugs away, but our new approach addresses that problem," McKenna said.
Researchers from the University of Southern California and Harvard discovered a novel way for a drug to zero in on damaged nerves and cells inside the ear, a remedy that could potentially restore the hearing of those who suffer from sensorineural hearing loss. (Bioconjug Chem. 2018;29[4]:1240.) They designed and tested a bisphosphonate conjugate of 7,8-Dihydroxyflavone (Ris-DHF), a known, potent agonist of the tropomyosin receptor kinase B that protects the cochlear spiral ganglion neurons (SGNs) from apoptosis. They found that Ris-DHF increases neurite outgrowth in vitro, maintains this ability after binding to hydroxyapatite, and regenerates synapses in kainic acid-damaged cochlear organ of Corti explants dissected in vitro with attached SGNs. Charles E. McKenna, a corresponding author for the study and chemistry professor at the USC Dornsife College of Letters, Arts and Sciences, said what's new here is they figured out how to deliver a drug into the inner ear so it actually stays put. "Inside this part of the ear, there's fluid constantly flowing that would sweep dissolved drugs away, but our new approach addresses that problem," McKenna said.