scholarly journals Mitochondrial Damage and Necroptosis in Aging Cochlea

2020 ◽  
Vol 21 (7) ◽  
pp. 2505
Author(s):  
Ah-Ra Lyu ◽  
Tae Hwan Kim ◽  
Sung Jae Park ◽  
Sun-Ae Shin ◽  
Seong-Hun Jeong ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Hair Cells ◽  
Neurodegenerative Disorder ◽  
Stria Vascularis ◽  
Mitochondrial Damage ◽  
Outer Hair Cells ◽  
Cochlear Blood Flow ◽  
Aged Mice ◽  
Age Related

Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.

scholarly journals Immunohistochemical localization of vimentin in the gerbil inner ear.

1989 ◽  
Vol 37 (12) ◽  
pp. 1787-1797 ◽  
Author(s):  
B A Schulte ◽  
J C Adams
Keyword(s):  
Epithelial Cells ◽  
Inner Ear ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Cell Types ◽  
Immunohistochemical Localization ◽  
Outer Hair Cells ◽  
Type I ◽  
Basal Cells

Cells containing immunoreactive vimentin-type intermediate filaments (IF) were identified in paraffin sections and whole-mount preparations of the gerbil inner ear. Most connective tissue cells showed positive immunostaining, although one unusual class of stromal cell lacked vimentin. Several different types of epithelial cells contained high levels of vimentin. In the cochlea, Deiters' cells, inner phalangeal cells, Boettcher's cells, some outer sulcus cells, and the intermediate cells of the stria vascularis showed strong immunoreactivity. Strial basal cells exhibited weaker and less consistent staining. Neither inner nor outer hair cells were stained. In the vestibular system, hair cells with a morphology and location more characteristic of type I than of type II cells showed strong immunostaining for vimentin. Supporting cells in vestibular neurosensory epithelium stained with less intensity. These results were surprising because epithelial cells in vivo only rarely express vimentin-type IF. Although the functional significance of vimentin remains to be established, its presence in some but not other highly specialized cell types provides an excellent marker for investigating the lineage and morphogenesis of the complex inner ear tissues.

scholarly journals Optimization of spectral-domain optical coherence tomography with a supercontinuum source for in vivo motion detection of low reflective outer hair cells in guinea pig cochleae

2021 ◽  
Author(s):  
Fumiaki Nin ◽  
Samuel Choi ◽  
Takeru Ota ◽  
Zhang Qi ◽  
Hiroshi Hibino
Keyword(s):  
Optical Coherence Tomography ◽  
High Resolution ◽  
Guinea Pig ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Acquisition Time ◽  
Total Acquisition Time ◽  
Sd Oct

AbstractSound evokes sub-nanoscale vibration within the sensory epithelium. The epithelium contains not only immotile cells but also contractile outer hair cells (OHCs) that actively shrink and elongate synchronously with the sound. However, the in vivo motion of OHCs has remained undetermined. The aim of this work is to perform high-resolution and -accuracy vibrometry in live guinea pigs with an SC-introduced spectral-domain optical coherence tomography system (SD-OCT). In this study, to reveal the effective contribution of SC source in the recording of the low reflective materials with the short total acquisition time, we compare the performances of the SC-introduced SD-OCT (SCSD-OCT) to that of the conventional SD-OCT. As inanimate comparison objects, we record a mirror, a piezo actuator, and glass windows. For the measurements in biological materials, we use in/ex vivo guinea pig cochleae. Our study achieved the optimization of a SD-OCT system for high-resolution in vivo vibrometry in the cochlear sensory epithelium, termed the organ of Corti, in mammalian cochlea. By introducing a supercontinuum (SC) light source and reducing the total acquisition time, we improve the axial resolution and overcome the difficulty in recording the low reflective material in the presence of biological noise. The high power of the SC source enables the system to achieve a spatial resolution of 1.72 ± 0.00 μm on a mirror and reducing the total acquisition time contributes to the high spatial accuracy of sub-nanoscale vibrometry. Our findings reveal the vibrations at the apical/basal region of OHCs and the extracellular matrix, basilar membrane.

scholarly journals A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Shankar J. Chinta ◽  
Subramanian Rajagopalan ◽  
Abirami Ganesan ◽  
Julie K. Andersen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Nitrosative Stress ◽  
Neurodegenerative Disorder ◽  
Oxidative And Nitrosative Stress ◽  
Prolyl Hydroxylases ◽  
Age Related

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB’s ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cellsin vitroin conjunction with reduced ROS production and activation of NFκB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NFκB activity and subsequent NO induction.In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB’s neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1.

scholarly journals Overexpression of SK2 Channels Enhances Efferent Suppression of Cochlear Responses Without Enhancing Noise Resistance

2007 ◽  
Vol 97 (4) ◽  
pp. 2930-2936 ◽  
Author(s):  
Stéphane F. Maison ◽  
Lisan L. Parker ◽  
Lucy Young ◽  
John P. Adelman ◽  
Jian Zuo ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Hair Cells ◽  
Otoacoustic Emissions ◽  
Outer Hair Cell ◽  
Outer Hair Cells ◽  
Sk Channels ◽  
Cochlear Function ◽  
Cochlear Hair Cells ◽  
Efferent Suppression

Cochlear hair cells express SK2, a small-conductance Ca2+-activated K+ channel thought to act in concert with Ca2+-permeable nicotinic acetylcholine receptors (nAChRs) α9 and α10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the α9/α10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in α9 overexpresser mice; however, in contrast to α9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca2+ entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility.

scholarly journals Olivocochlear suppression of outer hair cells in vivo: evidence for combined action of BK and SK2 channels throughout the cochlea

2013 ◽  
Vol 109 (6) ◽  
pp. 1525-1534 ◽  
Author(s):  
Stéphane F. Maison ◽  
Sonja J. Pyott ◽  
Andrea L. Meredith ◽  
M. Charles Liberman
Keyword(s):  
Hair Cells ◽  
In Vitro Study ◽  
Bk Channels ◽  
Outer Hair Cells ◽  
Cochlear Hair Cells ◽  
Α Subunit ◽  
Combined Action ◽  
Cholinergic Effects

Cholinergic inhibition of cochlear hair cells via olivocochlear (OC)-efferent feedback is mediated by Ca2+ entry through α9-/α10-nicotinic receptors, but the nature of the K+ channels activated by this Ca2+ entry has been debated (Yoshida N, Hequembourg SJ, Atencio CA, Rosowski JJ, Liberman MC. J Neurophysiol 85: 84–88, 2001). A recent in vitro study (Wersinger E, McLean WJ, Fuchs PA, Pyott SJ. PLoS One 5: e13836, 2010) suggests that small-conductance (SK2) channels mediate cholinergic effects in the apical turn, whereas large-conductance (BK) channels mediate basal turn effects. Here, we measure, as a function of cochlear frequency, the magnitude of BK and SK2 expression in outer hair cells and the strength of in vivo OC suppression in BK+/+ mice vs. BK−/− lacking the obligatory α-subunit (Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. J Biol Chem 279: 36746–36752, 2004). Except at the extreme apical tip, we see immunostaining for both BK and SK2 in BK+/+. Correspondingly, at all testable frequencies (8–45 kHz), we see evidence for both SK2 and BK contributions to OC effects evoked by electrically stimulating the OC bundle: OC-mediated suppression was reduced, but not eliminated, at all frequencies in the BK−/− ears. The suppression remaining in BK nulls was blocked by strychnine, suggesting involvement of α9-/α10-cholinergic receptors, coupled to activation of the remaining SK2 channels.

scholarly journals Aqueous Extract of Dendropanax morbiferus Leaves Effectively Alleviated Neuroinflammation and Behavioral Impediments in MPTP-Induced Parkinson’s Mouse Model

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shin-Young Park ◽  
Govindarajan Karthivashan ◽  
Hyun Myung Ko ◽  
Duk-Yeon Cho ◽  
Joonsoo Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Major Constituent ◽  
Bioactive Constituents ◽  
Endemic Plant ◽  
Leaf Extracts ◽  
Age Related ◽  
Dendropanax Morbifera

Parkinson’s disease (PD) is a commonly reported age-related neurodegenerative disorder. Microglial-mediated neuroinflammation is one of the cardinal hallmarks of various neurodegenerative disorders, including PD progression. Inadequate therapeutic strategies and substantial adverse effects of well-established drug candidates demand new therapeutic leads to treat PD. Dendropanax morbifera (DM) is an endemic plant species of South Korea, and it has been used extensively as traditional medicine to treat numerous clinical complications. In this study, we conducted an initial profiling of the few major phytoconstituents of aqueous DM leaf extracts (DML) and quantified the same using high-performance liquid chromatography tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS/MS). We subsequently evaluated the antineuroinflammatory activity and ameliorative potential of DML in both in vitro and in vivo experimental PD models. The prophylactic treatment of DML effectually improved the behavioral deficits, curbed the microglial-mediated neuroinflammation, and protected dopaminergic (DA) neuronal loss by restoring tyrosine hydroxylase (TH) levels in brain tissue of the MPTP-induced PD mouse model. We conducted chromatographic profiling and identified chlorogenic acid (CA) as a major constituent (19.5 mg/g of BuOH fraction), which has been well documented as an antioxidant and anti-inflammatory agent. This was found to be in harmony with our in vitro results, where DML suppressed the level of inflammatory mediators and allied the signaling pathway in LPS-stimulated microglial cells. The results of our study indicate that DML and its bioactive constituents can be developed as potential therapeutic candidates against progressive PD complications.

scholarly journals Age‐related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells

2020 ◽  
Vol 598 (18) ◽  
pp. 3891-3910 ◽  
Author(s):  
Jing‐Yi Jeng ◽  
Stuart L. Johnson ◽  
Adam J Carlton ◽  
Lara De Tomasi ◽  
Richard J. Goodyear ◽  
...  
Keyword(s):  
Hair Cells ◽  
Morphological Characteristics ◽  
Outer Hair Cells ◽  
Age Related ◽  
Age Related Changes

scholarly journals Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6664
Author(s):  
Stella Chin-Shaw Tsai ◽  
Kuender D. Yang ◽  
Kuang-Hsi Chang ◽  
Frank Cheau-Feng Lin ◽  
Ruey-Hwang Chou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Umbilical Cord ◽  
Hair Cells ◽  
Round Window ◽  
Outer Hair Cells ◽  
Protective Effects ◽  
Cochlear Hair Cells ◽  
Potential Applications ◽  
Round Window Niche

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Physiologically silent sodium channels in mammalian outer hair cells

1994 ◽  
Vol 72 (2) ◽  
pp. 1037-1040 ◽  
Author(s):  
C. M. Witt ◽  
H. Y. Hu ◽  
W. E. Brownell ◽  
D. Bertrand
Keyword(s):  
Sodium Channels ◽  
Hair Cells ◽  
Sodium Current ◽  
High Sensitivity ◽  
Outer Hair Cells ◽  
Inward Current ◽  
Cell Recording ◽  
Voltage Dependent

1. Voltage-dependent properties of isolated guinea pig outer hair cells (OHCs) were investigated using whole-cell recording. An inward current was detected in approximately 10% of the cells. This inward current was identified as belonging to the voltage-activated sodium current family on the basis of its high sensitivity to tetrodotoxin and the effect of substitution of impermeant ions. Although this is the first report of a sodium current in the mammalian cochlea, it differs from the classical neuronal sodium current by having a variable magnitude from cell to cell and an inactivation that is shifted to hyperpolarized potentials. The sensory processing role of hair cells in general and outer hair cells in particular could be disrupted by the presence of a regenerative voltage-dependent current. The functional role of the OHC sodium channels is puzzling, particularly as they may be silent in vivo.

In vivo noise exposure alters the in vitro motility and viability of outer hair cells

1991 ◽  
Vol 52 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Laurent Décory ◽  
Hakim Hiel ◽  
Jean-Marie Aran
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Outer Hair Cells ◽  
In Vitro Motility
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