In vivo delivery of Atoh1 gene to rat cochlea using a dendrimer-based nanocarrier.

Gene therapy is a promising clinical solution to hearing loss. However suitable gene carriers for the auditory system are currently unavailable. Given the unique structure of the inner ear, the route of delivery and gene transfer efficiency are still not optimal at present.

Modulation of Mcl-1 expression reduces age-related cochlear degeneration.

Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression.

Migration and differentiation of mouse embryonic stem cells transplanted into mature cochlea of rats with aminoglycoside-induced hearing loss.

Conclusion: Mouse embryonic stem cells (ESCs) transplanted into the scala tympani are able to migrate in the cochlea of rats deafened with aminoglycoside and partly restore the structure of sensory epithelia of the inner ear.

Objectives: To explore the migration and differentiation of enhanced green fluorescence protein (EGFP)-expressing ESCs by transplanting them into the scala tympani of rats with amikacin sulfate-induced hearing loss.

Methods: Adult Sprague-Dawley (SD) rats were deafened with amikacin sulfate.

Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.

The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability.

[Changes of gamma-amino butyric acid and electrophysiology inferior colliculus after noise exposure in guinea pig].

Objective: To explore the changes of inferior collicular (IC) neurons after noise exposure cochlea injury in guinea pig to elucidate the encoding mechanism of pure tones, observe the changes of IC gamma-amino butyric acid (GABA) after cochlear damage by acoustic trauma and understand the possible mechanism of symptoms such as noise-induced tinnitus, hyperacusis and loudness recruitment.

Methods: The responses of IC neurons to pure tone stimuli were observed in guinea pig at Day 1 and Days 11-21 after cochlear damage induced by noise exposure. And the IC neurons of normal guinea pig were assigned as the controls.

Induction of the chick columella and its integration with the inner ear.

Background: The auditory complex of the chick, like that of humans, is made of intimate and highly ordered connections between the inner ear, the middle ear, and the outer ear. Unlike mammals, the middle ear of chick has only one ossicle, known as the columella. The independent lineages of the two suggest that some mechanism must exist that ensures the connectivity between the inner ear and the columella; however, the basis of integration is not known.

Age-related changes in the ratio of Mcl-1/Bax expression in the rat cochlea.

Conclusion: Down-regulation of the ratio of Mcl-1/Bax expression may contribute to age-related sensory cell degeneration in the cochlea.

Objective: To better understand the involvement of Bcl-2 family members in the regulation of age-related sensory cell death, we examined the expression patterns of Bcl-2-associated protein X (Bax) and its suppressor, myeloid cell leukemia 1 (Mcl-1) in young and aging rat cochleae.

Methods: Young (2-3 months) and aging (27-28 months) Fischer rats were used.

Effects of DAPT and Atoh1 overexpression on hair cell production and hair bundle orientation in cultured Organ of Corti from neonatal rats.

Background: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure.

The differentiation of mesenchymal stem cells into inner ear hair cell-like cells in vitro.

Conclusion: Bone marrow mesenchymal stem cells (MSCs) have the ability to differentiate into hair cells, and this method of culturing MSCs provides a useful tool for studies on mammalian cochlear hair cell regeneration.

Objective: To investigate a method to induce bone marrow MSCs to differentiate into inner ear hair cells.

Methods: Rat bone marrow MSCs were isolated from healthy rats and cultured in vitro.