One example is auditory neuropathy, a variety of hearing loss in which the outer hair cells of the cochlea are intact and functioning, but sound information is not faithfully transmitted by the auditory nerve to the brain. (wikipedia.org)
These changes in micromechanics include depolymerization of actin filaments in stereocilia (in TTS), edema and swelling of stria vascularis, afferent nerve endings and supporting cells inside the cochlea. (drsanu.com)
When the noise exposure is so severe, a discrete but direct mechanical disruption results in a toxic mixing of endolymph and perilymph through microbreaks in the structural framework of the cochlear duct which leads to loss of hair cells and their corresponding nerve fibers. (drsanu.com)
Death of the sensory cell can lead to progressive Wallerian degeneration and loss of primary auditory nerve fibers. (drsanu.com)
All levels of the auditory system contribute to this sensitivity toward certain frequencies, from the outer ear's physical characteristics to the nerves and tracts that convey the nerve impulses of the auditory portion of the brain. (findmeacure.com)
VGLUT3-persistent neurons are small-diameter unmyelinated neurons that are further divided into two subtypes: (1) tyrosine hydroxylase (TH)-positive C-LTMRs that form the longitudinal lanceolate endings around hairs, and (2) TH-negative neurons that form epidermal-free nerve endings. (jneurosci.org)
Neurons5
This research is the first to produce induced pluripotent stem cell-derived inner ear sensory neurons in the Neurog1 +/− heterozygote mouse using blastocyst complementation. (biomedcentral.com)
Hearing depends on the mechano-sensory hair cells (HCs) and their innervating neurons, the spiral ganglionneurons (SGNs), which are responsible for transmitting auditory information from the HCs in the organ of Corti to the cochlear nucleus in the brainstem. (biomedcentral.com)
Using exogenous stem cells to replace lost inner ear neurons is a potential strategy if stem cell-derived neurons can form central and peripheral connections, form synapses on hair cells and cochlear nucleus neurons, and re-establish functional and tonotopic circuits [ 6 ]. (biomedcentral.com)
We address these potential limitations by adopting the technique of blastocyst complementation (BC) to generate inner ear neurons from induced pluripotent stem cells (iPSCs). (biomedcentral.com)
VGLUT3-transient neurons are large- or medium-diameter myelinated mechanoreceptors that form the Merkel cell-neurite complex. (jneurosci.org)
Cochlear4
Hearing loss related to age usually affects both ears and is due to cochlear hair cell loss. (wikipedia.org)
The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. (drsanu.com)
Outer hair cells of the cochlear are more susceptible to noise exposure than inner hair cells. (drsanu.com)
Other less explained, but identified metabolic cochlear mechanisms of NIHL includes outer hair cell plasma membrane fluidity , role of glucocorticoid receptors and oxidative stress . (drsanu.com)
Mice2
In baricitinib plus CsA treated mice, circulating CD4+T-bet+ T cells, CD8+T-bet+ T cells, and CD4+FOXP3+ regulatory T cells were reduced. (bvsalud.org)
Single cell RNA sequencing revealed a unique expression profile in immune cells in the skin of baricitinib plus CsA treated mice, including decreased inflammatory neutrophils and increased CCR2- macrophages. (bvsalud.org)
Inner ear2
This work validates the use of blastocyst complementation as a tool to create novel insight into the function of developmental genes and highlights blastocyst complementation as a potential platform for generating chimeric inner ear cell types that can be transplanted into damaged inner ears to improve hearing. (biomedcentral.com)
In parallel, his research program focuses on inner ear hair cell development and regeneration. (stanford.edu)
Degeneration2
Temporary threshold shift is also associated with buckling of supporting pillar cell bodies inside cochlea, while permanent shift is associated with focal hair cell loss and complete degeneration. (drsanu.com)
During residency, he undertook a two-year NIH-sponsored research fellowship investigating mechanisms of hair cell degeneration. (stanford.edu)
Differentiation2
Organogenesis is a complex developmental process requiring hierarchical cell and tissue differentiation, coordinated in time and space in response to changes in local and distant signaling cues. (biomedcentral.com)
The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the low efficacy of preclinical nonconformal radiotherapy (RT) for tumors. (bvsalud.org)
Hearing loss1
Noise induced hearing loss (NIHL) is defined as reduction in auditory acuity (hearing ability) associated with long term exposure to loud sounds. (drsanu.com)
Recruitment1
Contrary to non-CRT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages or dendritic cells but instead up-regulate major histocompatibility complex II and costimulatory molecules. (bvsalud.org)
Regeneration2
Kelley, M.W. (2013) Taking hair cell regeneration up a notch. (nih.gov)
Application of RGM antibodies in brain or axonal injury has led to neuronal and synaptic regeneration with functional recovery 3 . (nature.com)
Embryonic1
The hindbrain boundary cell population (BCP) is specified at the interface between adjacent compartments during embryonic development of the posterior brain. (upf.edu)
Pathways1
Kelley, M.W. (2013) Signaling pathways and commitment to cell fate. (nih.gov)
Neuroscience3
3 Institute for Auditory Neuroscience and Inner Ear Laboratory, University Medical Center Göttingen, 37073 Göttingen, Germany. (nih.gov)
5 Auditory Neuroscience Group, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany. (nih.gov)
7 Institute for Auditory Neuroscience and Inner Ear Laboratory, University Medical Center Göttingen, 37073 Göttingen, Germany, [email protected][email protected]. (nih.gov)
Sensory3
Puligilla, C., Kelley, M.W. (2017) Dual role for Sox2 in specification of sensory competence and regulation of Atoh1 function . (nih.gov)
The National Institute on Deafness and Other Communication Disorders (NIDCD) invites grant applications using comprehensive systems biology approaches intended to restore lost auditory hair cells and their sensory function following damage to the inner ear from a variety of factors including disease, aminoglycosides, noise, and aging. (nih.gov)
In the inner ear, sensory versus neuronal specification is achieved through few well-defined bHLH transcription factors. (upf.edu)
BHLH1
Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. (nih.gov)
Tissues3
This result is consistent with previous ultrastructural analyses of KA neurotoxicity in other neuronal tissues. (nature.com)
Background: Boundaries that prevent cell movement allow groups of cells to maintain their identity and follow independent developmental trajectories without the need for ongoing instructive signals from surrounding tissues. (upf.edu)
Cells in growing tissues receive both biochemical and physical cues from their microenvironment. (upf.edu)
Development2
Neuronal development requires Neurog1, followed by its downstream target Neurod1 , to cross-regulate Atoh1 expression. (nih.gov)
Ng, L., Kelley, M.W., and Forrest, D. (2013) Making sense with thyroid hormone-the role of T(3) in auditory development . (nih.gov)
Biology1
Following a post-doctoral fellowship at the University of Washington, he became an Assistant Professor in the Department of Cell Biology at Georgetown University in 1996. (nih.gov)
Fundamental1
Growing evidence has shown that mechanical signals are fundamental regulators of cell behavior. (upf.edu)
Inner hair1
Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy. (nature.com)
Type1
RGMs bind the type 1 transmembrane protein neogenin1, which controls axon guidance and neuronal survival effects. (nature.com)