Publications by authors named "Valeria C Castagna"
During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABA receptors (GABAR).
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- Cholesterol plays a crucial role in maintaining neuronal membrane integrity and proper function, and imbalances can lead to neurodegenerative diseases and age-related changes.
- This study investigates cholesterol levels in the inner ear of young and aged mice, finding that levels decrease with age, linked to increased expression of the cholesterol enzyme CYP46A1.
- Pharmacological activation of CYP46A1 with efavirenz reduces cholesterol in outer hair cells, negatively impacting hearing, but dietary phytosterol supplementation can help counteract this effect, suggesting a potential strategy for preventing hearing loss.
The genetic bases underlying the evolution of morphological and functional innovations of the mammalian inner ear are poorly understood. Gene regulatory regions are thought to play an important role in the evolution of form and function. To uncover crucial hearing genes whose regulatory machinery evolved specifically in mammalian lineages, we mapped accelerated noncoding elements (ANCEs) in inner ear transcription factor (TF) genes and found that PKNOX2 harbors the largest number of ANCEs within its transcriptional unit.
View Article and Find Full Text PDFPreventing presbycusis in mice with enhanced medial olivocochlear feedback.
Proc Natl Acad Sci U S A
May 2020
Article Synopsis
- Aging is the leading cause of hearing loss, with age-related hearing loss (ARHL) first impacting speech comprehension, especially in noisy environments.
- Research in mice shows that cochlear synaptic degeneration and hair cell loss occur with age, linked to changes in cholinergic receptors that affect auditory feedback.
- Mice with enhanced nicotinic receptors maintained better cochlear function, indicating that boosting olivocochlear feedback may help prevent age-related hearing decline.
The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this maturation process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells.
View Article and Find Full Text PDFThe mammalian inner ear possesses functional and morphological innovations that contribute to its unique hearing capacities. The genetic bases underlying the evolution of this mammalian landmark are poorly understood. We propose that the emergence of morphological and functional innovations in the mammalian inner ear could have been driven by adaptive molecular evolution.
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- - Cochlear synaptopathy, linked to loud noise exposure, leads to hidden hearing loss (HHL), affecting people's ability to understand speech in noisy situations, even without obvious changes in hearing sensitivity.
- - This study compares two mouse models (a knock-out with reduced cholinergic activity and a knock-in with enhanced cholinergic activity) to see how the medial olivocochlear (MOC) system affects HHL after noise exposure.
- - Results indicate that higher cholinergic activity helps protect against HHL and promotes the formation of new synapses in the inner ear, suggesting potential avenues for repairing damage from noise exposure.