Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice

Int J Mol Sci. 2021 Mar 11;22(6):2853. doi: 10.3390/ijms22062853.

Abstract

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

Keywords: age-related hearing loss; chronic oral treatment; hearing protection; mouse model; selegiline.

MeSH terms

  • Administration, Oral
  • Aging / physiology*
  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / pharmacology
  • Auditory Threshold / drug effects
  • Auditory Threshold / physiology
  • Disease Models, Animal*
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Hearing Loss, Sensorineural / drug therapy*
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Selegiline / administration & dosage
  • Selegiline / pharmacology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Antiparkinson Agents
  • Protective Agents
  • Selegiline