scholarly journals Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jin Chen ◽  
Yan Zhu ◽  
Chun Liang ◽  
Jing Chen ◽  
Hong-Bo Zhao
Keyword(s):  
Hearing Loss ◽  
Atp Release ◽  
Receptor Potential ◽  
Lateral Wall ◽  
Cell Loss ◽  
Endocochlear Potential ◽  
Potential Generation ◽  
Physiological Conditions ◽  
Auditory Receptor ◽  
Deficient Mice

Abstract Pannexin1 (Panx1) is a gap junction gene in vertebrates whose proteins mainly function as non-junctional channels on the cell surface. Panx1 channels can release ATP under physiological conditions and play critical roles in many physiological and pathological processes. Here, we report that Panx1 deficiency can reduce ATP release and endocochlear potential (EP) generation in the cochlea inducing hearing loss. Panx1 extensively expresses in the cochlea, including the cochlear lateral wall. We found that deletion of Panx1 in the cochlear lateral wall almost abolished ATP release under physiological conditions. Positive EP is a driving force for current through hair cells to produce auditory receptor potential. EP generation requires ATP. In the Panx1 deficient mice, EP and auditory receptor potential as measured by cochlear microphonics (CM) were significantly reduced. However, no apparent hair cell loss was detected. Moreover, defect of connexin hemichannels by deletion of connexin26 (Cx26) and Cx30, which are predominant connexin isoforms in the cochlea, did not reduce ATP release under physiological conditions. These data demonstrate that Panx1 channels dominate ATP release in the cochlea ensuring EP and auditory receptor potential generation and hearing. Panx1 deficiency can reduce ATP release and EP generation causing hearing loss.

scholarly journals Linalool odor‐induced analgesia is triggered by TRPA1-independent pathway in mice

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hideki Kashiwadani ◽  
Yurina Higa ◽  
Mitsutaka Sugimura ◽  
Tomoyuki Kuwaki
Keyword(s):  
Pain Threshold ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Analgesic Effects ◽  
Neuronal Mechanisms ◽  
Odor Exposure ◽  
Noxious Mechanical Stimulation ◽  
Transient Receptor ◽  
Deficient Mice

AbstractWe had recently reported that linalool odor exposure induced significant analgesic effects in mice and that the effects were disappeared in olfactory-deprived mice in which the olfactory epithelium was damaged, thus indicating that the effects were triggered by chemical senses evoked by linalool odor exposure. However, the peripheral neuronal mechanisms, including linalool receptors that contribute toward triggering the linalool odor-induced analgesia, still remain unexplored. In vitro studies have shown that the transient receptor potential ankyrin 1 (TRPA1) responded to linalool, thus raising the possibility that TRPA1 expressed on the trigeminal nerve terminal detects linalool odor inhaled into the nostril and triggers the analgesic effects. To address this hypothesis, we measured the behavioral pain threshold for noxious mechanical stimulation in TRPA1-deficient mice. In contrast to our expectation, we found a significant increase in the threshold after linalool odor exposure in TRPA1-deficient mice, indicating the analgesic effects of linalool odor even in TRPA1-deficient mice. Furthermore, intranasal application of TRPA1 selective antagonist did not alter the analgesic effect of linalool odor. These results showed that the linalool odor-induced analgesia was triggered by a TRPA1-independent pathway in mice.

scholarly journals Predominant neuronal B-cell loss in L5 DRG of p75 receptor-deficient mice

2002 ◽  
Vol 200 (1) ◽  
pp. 81-87 ◽  
Author(s):  
M. Dreetz Gjerstad ◽  
T. Tandrup ◽  
M. Koltzenburg ◽  
J. Jakobsen
Keyword(s):  
B Cell ◽  
Cell Loss ◽  
P75 Receptor ◽  
Deficient Mice

scholarly journals Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

scholarly journals Noise-induced and age-related hearing loss:  new perspectives and potential therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 927 ◽  
Author(s):  
M Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Cell Loss ◽  
Sensorineural Hearing ◽  
Hair Cell Loss ◽  
Age Related ◽  
Age Related Hearing Loss

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

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