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Scientific Reports Nov 2023Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has...
Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has been extensively studied by confocal microscopy, however, understanding the nature and sequence of damage requires ultrastructural analysis. Here, we used focused ion-beam scanning electron microscopy to mill, image, segment and reconstruct ANF terminals in mice, 1 day and 1 week after synaptopathic exposure (8-16 kHz, 98 dB SPL). At both survivals, ANF terminals were normal in number, but 62% and 53%, respectively, lacked normal synaptic specializations. Most non-synapsing fibers (57% and 48% at 1 day and 1 week) remained in contact with an IHC and contained healthy-looking organelles. ANFs showed a transient increase in mitochondrial content (51%) and efferent innervation (34%) at 1 day. Fibers maintaining synaptic connections showed hypertrophy of pre-synaptic ribbons at both 1 day and 1 week. Non-synaptic fibers were lower in mitochondrial content and typically on the modiolar side of the IHC, where ANFs with high-thresholds and low spontaneous rates are normally found. Even 1 week post-exposure, many ANF terminals remained in IHC contact despite loss of synaptic specializations, thus, regeneration efforts at early post-exposure times should concentrate on synaptogenesis rather than neurite extension.
Topics: Mice; Animals; Cochlea; Noise; Hearing Loss, Noise-Induced; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Synapses; Cochlear Nerve; Auditory Threshold
PubMed: 37945811
DOI: 10.1038/s41598-023-46859-6 -
Science Advances Oct 2023We present an adaptive optical neural network based on a large-scale event-driven architecture. In addition to changing the synaptic weights (synaptic plasticity), the...
We present an adaptive optical neural network based on a large-scale event-driven architecture. In addition to changing the synaptic weights (synaptic plasticity), the optical neural network's structure can also be reconfigured enabling various functionalities (structural plasticity). Key building blocks are wavelength-addressable artificial neurons with embedded phase-change materials that implement nonlinear activation functions and nonvolatile memory. Using multimode focusing, the activation function features both excitatory and inhibitory responses and shows a reversible switching contrast of 3.2 decibels. We train the neural network to distinguish between English and German text samples via an evolutionary algorithm. We investigate both the synaptic and structural plasticity during the training process. On the basis of this concept, we realize a large-scale network consisting of 736 subnetworks with 16 phase-change material neurons each. Overall, 8398 neurons are functional, highlighting the scalability of the photonic architecture.
PubMed: 37862413
DOI: 10.1126/sciadv.adi9127 -
Medicina (Kaunas, Lithuania) Nov 2023There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur... (Review)
Review
There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.
Topics: Humans; Neurobiology; Polyphenols; Cochlea; Aging; Deafness
PubMed: 38004094
DOI: 10.3390/medicina59112045 -
Animals : An Open Access Journal From... Jun 2023Guide dogs work for extended periods and are exposed to multiple environmental stimuli that could lead to higher stress compared with companion dogs. Cortisol is the...
Guide dogs work for extended periods and are exposed to multiple environmental stimuli that could lead to higher stress compared with companion dogs. Cortisol is the main hormone associated with stress in most mammals. This study included seven guide dogs and seven same-breed dogs that were trained as guide dogs but became companion dogs to compare their salivary cortisol levels before, during, and after a period of social isolation and exposure to a 110-decibel gunshot sound. Each dog was left alone in an empty room for 60 min. After 15 min, the dogs were exposed to the sound. We collected four saliva samples from each dog. The first one was taken 5 min before starting the social isolation period, and the following ones at 15, 30, and 45 min after the test started. A two-way ANOVA was used to compare the group effect and the time effect during isolation and noise exposure. The results showed higher levels of cortisol in the guide dogs compared with the companion dogs throughout the test. No differences were found in time or in the interaction between time and group. This suggests that being a guide dog increases levels of basal cortisol when compared with dogs that live as companion animals and family members.
PubMed: 37370493
DOI: 10.3390/ani13121981 -
Biomedicine & Pharmacotherapy =... Jul 2023No medical interventions for noise induced hearing loss (NIHL) are approved by the Food and Drug Administration (USA). Here, we evaluate statins in CBA/CaJ mice as...
No medical interventions for noise induced hearing loss (NIHL) are approved by the Food and Drug Administration (USA). Here, we evaluate statins in CBA/CaJ mice as potential drugs for hearing loss. Direct delivery of fluvastatin to the cochlea and oral delivery of lovastatin were evaluated. Baseline hearing was assessed using Auditory Brain Stem Responses (ABRs). For fluvastatin, a cochleostomy was surgically created in the basal turn of the cochlea by a novel, laser-based procedure, through which a catheter attached to a mini-osmotic pump was inserted. The pump was filled with a solution of 50 µM fluvastatin+carrier or with the carrier alone for continuous delivery to the cochlea. Mice were exposed to one octave band noise (8-16 kHz x 2 h x 110 dB SPL). In our past work with guinea pigs, fluvastatin protected in the contralateral cochlea. In this study in CBA/CaJ mice, hearing was also assessed in the contralateral cochlea 1-4 weeks after noise exposure. At two weeks post exposure, ABR thresholds at 4, 8, 12, 16, and 32 kHz were elevated, as expected, in the noise+carrier alone treated mice by approximately 9-, 17-, 41-, 29-, and 34-dB, respectively. Threshold elevations were smaller in mice treated with noise+fluvastatin to about 2-, 6-, 20-,12- and 12-dB respectively. Survival of inner hair cell synapses were not protected by fluvastatin over these frequencies. Lovastatin delivered by gavage showed lower threshold shifts than with carrier alone. These data show that direct and oral statin delivery protects mice against NIHL.
Topics: United States; Mice; Animals; Guinea Pigs; Mice, Inbred CBA; Hearing Loss, Noise-Induced; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fluvastatin; Lovastatin; Excipients
PubMed: 37435721
DOI: 10.1016/j.biopha.2023.114674