Project description:In order to elucidate molecular mechanisms of noise-induced hearing loss and dexamethasone therapy in the cochlea (inner ear), transcriptome of cochlear samples was analyzed after induction of hearing loss by exposure to intense noise in mice. Dexamethasone was intraperitoneally injected immediately following the noise trauma. Cochlear transcriptome was analyzed at 12h and 24h following the noise trauma and dexamethasone administration.
Project description:In order to elucidate molecular mechanisms of noise-induced hearing loss in the cochlea (inner ear), transcriptome of the cochlear sample was analyzed after induction of hearing loss by exposure to intense noise in mice. Cochlear transcriptome was analyzed at 3 hours following the noise exposure.
Project description:Six month-old wild type and Igf1 heterozygous mice were exposed to a violet swept sine noise (frequency range 2–20 kHz) at 110 dB SPL for 30 minutes. Cochlear samples were taken at 2 and 24 hours post-noise exposure to study the evolution of the expression of inflammation genes by using PCR arrays and RT-qPCR. Six month-old wild type and Igf1 heterozygous mice not exposed to noise were used as control.
Project description:Six month-old wild type and Igf1 heterozygous mice were exposed to a violet swept sine noise (frequency range 2–20 kHz) at 110 dB SPL for 30 minutes. Cochlear samples were taken at 2 and 24 hours post-noise exposure to study the evolution of the expression of inflammation genes by using PCR arrays and RT-qPCR. Six month-old wild type and Igf1 heterozygous mice not exposed to noise were used as control.
Project description:The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses.
Project description:The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses.
