Early functional alterations in membrane properties and neuronal degeneration are hallmarks of progressive hearing loss in NOD mice

• Published in: Scientific reports 2019-08, Vol.9 (1), p.12128-17, Article 12128
• Main Authors: Lee, Jeong Han, Park, Seojin, Perez-Flores, Maria C., Wang, Wenying, Kim, Hyo Jeong, Izu, Leighton, Gratton, Michael Anne, Chiamvimonvat, Nipavan, Yamoah, Ebenezer N.
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 631/378/2619/1387; 64/110; 64/60; 692/699/375/365; 9/30; 9/74; 96/35; 96/63; Action potential; Aging; Aging - pathology; Aging - physiology; Animals; Axons; Cations, Monovalent - metabolism; Cells, Cultured; Cochlea; Diabetes mellitus; Disease Models, Animal; Disease Progression; Ear, Inner - pathology; Ear, Inner - physiopathology; Etiology; Evoked Potentials, Auditory, Brain Stem - physiology; Excitability; Female; Hair; Hair cells; Hearing loss; Hearing Loss, Sensorineural - pathology; Hearing Loss, Sensorineural - physiopathology; Hearing protection; Human populations; Humanities and Social Sciences; Latency; Longitudinal Studies; Male; Membrane conductance; Membrane potential; Membrane Potentials - physiology; Membranes; Mice, Inbred ICR; Mice, Inbred NOD; Mice, Transgenic; multidisciplinary; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neurodegeneration; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - physiopathology; Neurons - pathology; Neurons - physiology; Potassium - metabolism; Potassium currents; Science; Science (multidisciplinary); Sensory neurons; Spiral ganglion; Synapses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48376-x

Presbycusis or age-related hearing loss (ARHL) is the most common sensory deficit in the human population. A substantial component of the etiology stems from pathological changes in sensory and non-sensory cells in the cochlea. Using a non-obese diabetic (NOD) mouse model, we have characterized changes in both hair cells and spiral ganglion neurons that may be relevant for early signs of age-related hearing loss (ARHL). We demonstrate that hair cell loss is preceded by, or in parallel with altered primary auditory neuron functions, and latent neurite retraction at the hair cell-auditory neuron synapse. The results were observed first in afferent inner hair cell synapse of type I neurites, followed by type II neuronal cell-body degeneration. Reduced membrane excitability and loss of postsynaptic densities were some of the inaugural events before any outward manifestation of hair bundle disarray and hair cell loss. We have identified profound alterations in type I neuronal membrane properties, including a reduction in membrane input resistance, prolonged action potential latency, and a decrease in membrane excitability. The resting membrane potential of aging type I neurons in the NOD, ARHL model, was significantly hyperpolarized, and analyses of the underlying membrane conductance showed a significant increase in K + currents. We propose that attempts to alleviate some forms of ARHL should include early targeted primary latent neural degeneration for effective positive outcomes.