ABSTRACT
G9a is essential for dendritic plasticity and is associated with neurological disorders. The possible relationship between age-related hearing loss and G9a expression in the auditory cortex has not been fully explored. This study aimed to understand the expression patterns of G9a-mediated histone methylations in the auditory cortex during aging. Using immunofluorescence and western blotting, we demonstrated that a significant reduction in G9a expression observed in the auditory cortex of 24-month-old rats compared to 3-month-old rats, was associated with remarkable hearing threshold elevation and hair cell loss. Correspondingly, histone H3 lysine 9 (H3K9) mono- and dimethylation (marked by H3K9me1 and H3K9me2, respectively), which were regulated by G9a activity, also evidently decreased during aging. These findings, which merit further investigation, suggest a possible association between G9a-mediated histone methylations and central age-related hearing disorders.
Subject(s)
Auditory Cortex/metabolism , Histone-Lysine N-Methyltransferase/genetics , Nerve Tissue Proteins/genetics , Presbycusis/genetics , Aging/genetics , Aging/metabolism , Animals , Auditory Threshold , Down-Regulation , Gene Expression Regulation , Hair Cells, Auditory/pathology , Histone Code , Histone-Lysine N-Methyltransferase/biosynthesis , Histones/metabolism , Male , Methylation , Models, Animal , Nerve Tissue Proteins/biosynthesis , Presbycusis/metabolism , Presbycusis/pathology , Protein Processing, Post-Translational , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the histological changes in the vestibular endorgans of Smad4 gene conditional knockout mice and to explore the influence of the Smad4 gene on vestibular development. METHODS: Histological changes of periphery vestibular organs in inner ear of Smad4 conditional knockout mice were investigated by frozen sections, immunofluorescence, confocal microscopy, scanning electron microscopy and transmission electron microscopy. RESULTS: There was no Smad4 expression in the inner ear cartilage capsule of Smad4-/- mice. In Smad4+/- mice, Smad4 expression in the same cartilage capsule was positive, and it was strong positive in Smad4+/+ mice. Smad4 expression in vestibular sense epithelium, crista ampullaris and macula, was positive. And no difference was found among these three genotypes. Studying at scanning electron microscopy and transmission electron microscopy levels and anti-filament immunofluorescence showed that no pathological changes were observed in all the three genotype mice. CONCLUSION: Although the Smad4 gene was knockout effectively in the auricular cartilage capsule of Smad4 conditional knockout mice,the histological changes of Smad4 conditional knockout mice in vestibulum auris internal were slightly.
Subject(s)
Ear, Inner/anatomy & histology , Smad4 Protein/genetics , Vestibule, Labyrinth/anatomy & histology , Animals , Ear, Inner/pathology , Genotype , Mice , Mice, Knockout , Vestibule, Labyrinth/pathologyABSTRACT
The regulation of the bone morphogenetic protein (BMP) signal transduction pathway is important in the development of the inner ear and vestibular system. We reported previously that small mothers against decapentaplegic homolog-4 (Smad4) is required for inner ear cochlear development and normal auditory function in mammals; however, the distribution and functional mechanisms of Smad4 at various stages of vestibular development remained unclear. To investigate the relationship between the Smad4 gene and vestibular organ development, we measured changes in the expression of BMP4 and Smad4 during vestibular development in C57BL/6 mice. In addition, vestibular structures, pathologic changes, and the vestibular function of chondrocyte-specific Smad4 knockout mice were compared to those of the control group. We found that the expression of Smad4 in the inner ear was delayed compared with that of BMP4. Moreover, chondrocyte-specific Smad4 knockout homozygous mice showed stunted growth and partial vestibular deformities, but it showed less histologic changes in the vestibular end-organs and saccule dysfunction. These results suggest that Smad4 participates in late-stage shaping of the configuration of the vestibule and development of vestibular functional, but a Smad4-independent pathway for the inner ear vestibular BMP4 signal transduction could not be rule out.
Subject(s)
Smad4 Protein/metabolism , Vestibule, Labyrinth/anatomy & histology , Vestibule, Labyrinth/embryology , Vestibule, Labyrinth/physiology , Animals , Behavior, Animal/physiology , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Evoked Potentials/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Signal Transduction/physiology , Smad4 Protein/geneticsABSTRACT
OBJECTIVE: To explore the distributing and changes of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) in obstructive sleep apnea and hypopnea syndrome (OSAHS). METHODS: This study investigated the content of NO and CGRP in plasma and in pharyngeal tissues of OSAHS subjects. Moreover, the distribution of NOS and CGRP in pharyngeal tissues was researched using method of immunohistochemistry. RESULTS: (1) Plasma NO level in control group was higher than in mild OSAHS group and in serious OSAHS group, P < 0.001. There was a significant increase in plasma CGRP after UPPP (P < 0.001), and the plasma CGRP level in control group was as high as that in after UPPP group (P > 0.05) NO level in pharyngeal tissue of OSAHS increased significantly, P < 0.001), but CGRP level decreased markedly, P < 0.001. (2) Immunohistochemistry change about NOS: there was a feeble positive expression in mucosa squamous epithelium of OSAHS and powerful positive expression in some salivary glandular epithelium, striated muscle cells, vascular wall/small vascular wall and epithelium of glandular duct of OSAHS. (3) Immunohistochemistry change about CGRP: There were diffusible positive markings in striated muscle cells and most cilium columnar epithelium in OSAHS, and negative expressions in other sites. CONCLUSIONS: (1) Circulating NO and CGRP are suppressed in OSAHS, and reversible promptly after UPPP. Further more, The content of NO in pharyngeal tissues increases significantly and that of CGRP decreases markedly. (2) The distribution of NOS and CGRP in pharyngeal tissue changes apparently according to sites.