keyword
https://read.qxmd.com/read/38500536/early-onset-hearing-loss-in-mouse-models-of-alzheimer-s-disease-and-increased-dna-damage-in-the-cochlea
#1
JOURNAL ARTICLE
Jae-Hyeon Park, Burcin Duan Sahbaz, Komal Pekhale, Xixia Chu, Mustafa N Okur, Mhamed Grati, Kevin Isgrig, Wade Chien, Elena Chrysostomou, Lauren Sullivan, Deborah L Croteau, Uri Manor, Vilhelm A Bohr
There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ+/- . The 3xTgAD/Polβ+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes...
2024: Aging Biol
https://read.qxmd.com/read/38481472/light-dependent-regulation-of-neurotransmitter-release-from-rod-photoreceptor-ribbon-synapses-involves-an-interplay-of-complexin-4-and-transducin-with-the-snare-complex
#2
JOURNAL ARTICLE
Uwe Thorsten Lux, Jutta Meyer, Olaf Jahn, Adam Davison, Norbert Babai, Andreas Gießl, Anna Wartenberg, Heinrich Sticht, Nils Brose, Kerstin Reim, Johann Helmut Brandstätter
Adaptation of photoreceptor sensitivity to varying light intensities is a fundamental requirement for retinal function and vision. Adaptive mechanisms in signal transduction are well described, but little is known about the mechanisms that adapt the photoreceptor synapse to changing light intensities. The SNARE complex regulators Complexin 3 and Complexin 4 have been proposed to be involved in synaptic light adaptation by limiting synaptic vesicle recruitment and fusion. How this Complexin effect is exerted is unknown...
2024: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/38473985/cochlear-ribbon-synapses-in-aged-gerbils
#3
JOURNAL ARTICLE
Sonny Bovee, Georg M Klump, Sonja J Pyott, Charlotte Sielaff, Christine Köppl
In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear...
February 27, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38430700/thyroid-hormone-controls-the-timing-of-cochlear-ribbon-synapse-maturation
#4
JOURNAL ARTICLE
Chaorong Yu, Yihan He, Qing Liu, Xiaoyun Qian, Xia Gao, Deye Yang, Ye Yang, Guoqiang Wan
Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice...
February 21, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38408870/cone-synaptic-function-is-modulated-by-the-leucine-rich-repeat-lrr-adhesion-molecule-lrfn2
#5
JOURNAL ARTICLE
Nazarul Hasan, Ronald G Gregg
Daylight vision is mediated by cone photoreceptors in vertebrates, which synapse with bipolar cells (BCs) and horizontal (HCs) cells. This cone synapse is functionally and anatomically complex, connecting to 8 types of depolarizing BCs (DBCs) and 5 types of hyperpolarizing BCs (HBCs) in mice. The dendrites of DBCs and HCs cells make invaginating ribbon synapses with the cone axon terminal, while HBCs form flat synapses with the cone pedicles. The molecular architecture that underpins this organization is relatively poorly understood...
February 26, 2024: ENeuro
https://read.qxmd.com/read/38395146/abnormal-%C3%AE-synuclein-aggregates-cause-synaptic-and-microcircuit-specific-deficits-in-the-retinal-rod-pathway
#6
JOURNAL ARTICLE
Tao Xu, Xin Liu, Xin Lin, Jiayi Xiao, Di Zhang, Fenfen Ye, Fan Lu, Jia Qu, Jun Zhang, Jiang-Fan Chen
α-Synuclein (α-Syn) is a key determinator of Parkinson disease (PD) pathology, but synapse and microcircuit pathologies in the retina underlying visual dysfunction are poorly understood. Using the old transgenic M83 PD model (mice aged 16 to 18 months) coupled with histochemical and ultrastructural analyses and ophthalmologic measurements, we revealed that abnormal α-Syn aggregation in the outer plexiform layer (OPL) was associated with degeneration in the CtBP2+ ribbon synapses of photoreceptor terminals and protein kinase Cα+ rod bipolar cell terminals, whereas α-Syn aggregates in the inner retina correlated with the reduction and degeneration of tyrosine hydroxylase- and parvalbumin-positive amacrine cells...
February 21, 2024: American Journal of Pathology
https://read.qxmd.com/read/38339191/a-novel-cre-recombinase-mouse-strain-for-cell-specific-deletion-of-floxed-genes-in-ribbon-synapse-forming-retinal-neurons
#7
JOURNAL ARTICLE
Shweta Suiwal, Philipp Wartenberg, Ulrich Boehm, Frank Schmitz, Karin Schwarz
We generated a novel Cre mouse strain for cell-specific deletion of floxed genes in ribbon synapse-forming retinal neurons. Previous studies have shown that the RIBEYE promotor targets the expression of recombinant proteins such as fluorescently tagged RIBEYE to photoreceptors and retinal bipolar cells and generates fluorescent synaptic ribbons in situ in these neurons. Here, we used the same promotor to generate a novel transgenic mouse strain in which the RIBEYE promotor controls the expression of a Cre-ER(T2) recombinase (RIBEYE-Cre)...
February 5, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38322575/ros-induced-oxidative-stress-and-mitochondrial-dysfunction-a-possible-mechanism-responsible-for-noise-induced-ribbon-synaptic-damage
#8
JOURNAL ARTICLE
Zi-Jing Yang, Chun-Li Zhao, Wen-Qi Liang, Zhong-Rui Chen, Zheng-De Du, Shu-Sheng Gong
Evidence suggests that damage to the ribbon synapses (RS) may be the main cause of auditory dysfunction in noise-induced hearing loss (NIHL). Oxidative stress is implicated in the pathophysiology of synaptic damage. However, the relationship between oxidative stress and RS damage in NIHL remains unclear. To investigate the hypothesis that noise-induced oxidative stress is a key factor in synaptic damage within the inner ear, we conducted a study using mice subjected to single or repeated noise exposure (NE)...
2024: American Journal of Translational Research
https://read.qxmd.com/read/38313060/spatial-patterns-of-noise-induced-inner-hair-cell-ribbon-loss-in-the-mouse-mid-cochlea
#9
JOURNAL ARTICLE
Yan Lu, Jing Liu, Bei Li, Haoyu Wang, Fangfang Wang, Shengxiong Wang, Hao Wu, Hua Han, Yunfeng Hua
In the mammalian cochlea, moderate acoustic overexposure leads to loss of ribbon-type synapse between the inner hair cell (IHC) and its postsynaptic spiral ganglion neuron (SGN), causing a reduced dynamic range of hearing but not a permanent threshold elevation. A prevailing view is that such ribbon loss (known as synaptopathy) selectively impacts the low-spontaneous-rate and high-threshold SGN fibers contacting predominantly the modiolar IHC face. However, the spatial pattern of synaptopathy remains scarcely characterized in the most sensitive mid-cochlear region, where two morphological subtypes of IHC with distinct ribbon size gradients coexist...
February 16, 2024: IScience
https://read.qxmd.com/read/38223931/hippo-cell-signaling-and-hs-proteoglycans-regulate-tissue-form-and-function-age-dependent-maturation-extracellular-matrix-remodelling-and-repair
#10
REVIEW
James Melrose
This review examined how Hippo cell signaling and HS-proteoglycans (HSPGs) regulate tissue form and function. Despite being a non-weight bearing tissue the brain is regulated by Hippo mechanoresponsive cell signalling pathways during embryonic development. HS-proteoglycans interact with growth factors, morphogens and extracellular matrix components to regulate development and pathology. Pikachurin and Eyes Shut interact with dystroglycan to stabilize the photoreceptor axoneme primary cilium and ribbon synapse facilitating phototransduction and neurotransduction with bipolar retinal neuronal networks in ocular vision, the primary human sense...
January 15, 2024: American Journal of Physiology. Cell Physiology
https://read.qxmd.com/read/38192121/light-and-electron-microscopic-observations-on-retinal-neurons-of-red-tail-shark-epalzeorhynchos-bicolor-h-m-smith-1931
#11
JOURNAL ARTICLE
Doaa M Mokhtar, Alessio Alesci, Simona Pergolizzi, Giacomo Zaccone
The structure of photoreceptors (PR) and the arrangement of neurons in the retina of red-tail shark were investigated using light and electron microscopy. The PR showed a mosaic arrangement and included double cones, single cones (SC), and single rods. Most cones occur as SC. The ratio between the number of cones and rods was 3:1.39 (±0.29). The rods were tall that reached the pigmented epithelium. The outer plexiform layer (OPL) showed a complex synaptic connection between the horizontal and photoreceptor terminals that were surrounded by Müller cell processes...
January 8, 2024: Microscopy Research and Technique
https://read.qxmd.com/read/38182732/snap-25-but-not-snap-23-is-essential-for-photoreceptor-development-survival-and-function-in-mice
#12
JOURNAL ARTICLE
Mengjia Huang, Chun Hin Chow, Akshay Gurdita, Hidekiyo Harada, Victor Q B Pham Truong, Sarah Eide, Hong-Shuo Sun, Zhong-Ping Feng, Philippe P Monnier, Valerie A Wallace, Shuzo Sugita
SNARE-mediated vesicular transport is thought to play roles in photoreceptor glutamate exocytosis and photopigment delivery. However, the functions of Synaptosomal-associated protein (SNAP) isoforms in photoreceptors are unknown. Here, we revisit the expression of SNAP-23 and SNAP-25 and generate photoreceptor-specific knockout mice to investigate their roles. Although we find that SNAP-23 shows weak mRNA expression in photoreceptors, SNAP-23 removal does not affect retinal morphology or vision. SNAP-25 mRNA is developmentally regulated and undergoes mRNA trafficking to photoreceptor inner segments at postnatal day 9 (P9)...
January 5, 2024: Communications Biology
https://read.qxmd.com/read/38168344/role-of-ribeye-pxdls-t-binding-cleft-in-normal-synaptic-ribbon-function
#13
Jie Zhu, Caixia Lv, Diane Henry, Stephen Viviano, Joseph Santos-Sacchi, Gary Matthews, David Zenisek
UNLABELLED: Non-spiking sensory hair cells of the auditory and vestibular systems encode a dynamic range of graded signals with high fidelity by vesicle exocytosis at ribbon synapses. Ribeye, the most abundant protein in the synaptic ribbon, is composed of a unique A domain specific for ribbons and a B-domain nearly identical to the transcriptional corepressor CtBP2. CTBP2 and the B-domain of Ribeye contain a surface cleft that binds to proteins harboring a PXDLS/T peptide motif. Little is known about the importance of this binding site in synaptic function...
December 12, 2023: bioRxiv
https://read.qxmd.com/read/38128648/proteomic-analysis-reveals-the-composition-of-glutamatergic-organelles-of-auditory-inner-hair-cell
#14
JOURNAL ARTICLE
Andreia P Cepeda, Momchil Ninov, Jakob Neef, Iwan Parfentev, Kathrin Kusch, Ellen Reisinger, Reinhard Jahn, Tobias Moser, Henning Urlaub
In the ear, inner hair cells (IHCs) employ sophisticated glutamatergic ribbon synapses with afferent neurons to transmit auditory information to the brain. The presynaptic machinery responsible for neurotransmitter release in IHC synapses includes proteins such as the multi-C2 -domain protein otoferlin and the vesicular glutamate transporter 3 (VGluT3). Yet, much of this likely unique molecular machinery remains to be deciphered. The scarcity of material has so far hampered biochemical studies which require large amounts of purified sample...
December 19, 2023: Molecular & Cellular Proteomics: MCP
https://read.qxmd.com/read/38118309/zinc-deficiency-triggers-hearing-loss-by-reducing-ribbon-synapses-of-inner-hair-cells-in-cba-n-mice
#15
JOURNAL ARTICLE
Myungjoo Shim, Junyeong Yi, Jhang Ho Pak, Jong Woo Chung
Zinc plays a vital role in our metabolism, encompassing antioxidant regulation, immune response, and auditory function. Several studies have reported that zinc levels correlate with hearing loss. We have previously demonstrated that the auditory brainstem response (ABR) threshold increased in mice fed a zinc-deficient diet. However, the effects of zinc deficiency on hearing were not fully elucidated. The present study investigated whether zinc deficiency affects hearing in association with neuronal components or cochlear structures...
December 16, 2023: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38101494/gentamicin-administration-leads-to-synaptic-dysfunction-in-inner-hair-cells
#16
JOURNAL ARTICLE
Gen Li, Yunge Gao, Hao Wu, Ting Zhao
Ototoxicity is a major side effect of aminoglycosides, which can cause irreversible hearing loss. Previous studies on aminoglycoside-induced ototoxicity have primarily focused on the loss of sensory hair cells. Recent investigations have revealed that aminoglycosides can also lead to the loss of ribbon synapses in inner hair cells (IHCs). However, the functional implications of ribbon synapse loss and the underlying mechanisms remain unclear. In this study, we intraperitoneally injected C57BL/6 J mice with 300 mg/kg gentamicin once daily for 3, 10, and 20 days...
January 2024: Toxicology Letters
https://read.qxmd.com/read/38099150/trophoblast-glycoprotein-is-required-for-efficient-synaptic-vesicle-exocytosis-from-retinal-rod-bipolar-cells
#17
JOURNAL ARTICLE
Colin M Wakeham, Qing Shi, Gaoying Ren, Tammie L Haley, Robert M Duvoisin, Henrique von Gersdorff, Catherine W Morgans
INTRODUCTION: Rod bipolar cells (RBCs) faithfully transmit light-driven signals from rod photoreceptors in the outer retina to third order neurons in the inner retina. Recently, significant work has focused on the role of leucine-rich repeat (LRR) proteins in synaptic development and signal transduction at RBC synapses. We previously identified trophoblast glycoprotein (TPBG) as a novel transmembrane LRR protein localized to the dendrites and axon terminals of RBCs. METHODS: We examined the effects on RBC physiology and retinal processing of TPBG genetic knockout in mice using immunofluorescence and electron microscopy, electroretinogram recording, patch-clamp electrophysiology, and time-resolved membrane capacitance measurements...
2023: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/38076928/auditory-hair-cells-and-spiral-ganglion-neurons-regenerate-synapses-with-refined-release-properties-in-vitro
#18
Philippe F Y Vincent, Eric D Young, Albert S B Edge, Elisabeth Glowatzki
Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing 'synaptopathy' and hearing loss. Co-cultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that newly formed IHC synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents...
December 2, 2023: bioRxiv
https://read.qxmd.com/read/38026697/the-first-synapse-in-vision-in-the-aging-mouse-retina
#19
JOURNAL ARTICLE
Kaspar Gierke, Uwe Thorsten Lux, Hanna Regus-Leidig, Johann Helmut Brandstätter
Vision is our primary sense, and maintaining it throughout our lifespan is crucial for our well-being. However, the retina, which initiates vision, suffers from an age-related, irreversible functional decline. What causes this functional decline, and how it might be treated, is still unclear. Synapses are the functional hub for signal transmission between neurons, and studies have shown that aging is widely associated with synaptic dysfunction. In this study, we examined the first synapse of the visual system - the rod and cone photoreceptor ribbon synapse - in the mouse retina using light and electron microscopy at 2-3 months, ~1 year, and >2 years of age...
2023: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/38019860/ca-2-regulation-of-glutamate-release-from-inner-hair-cells-of-hearing-mice
#20
JOURNAL ARTICLE
Lina María Jaime Tobón, Tobias Moser
In our hearing organ, sound is encoded at ribbon synapses formed by inner hair cells (IHCs) and spiral ganglion neurons (SGNs). How the underlying synaptic vesicle (SV) release is controlled by Ca2+ in IHCs of hearing animals remained to be investigated. Here, we performed patch-clamp SGN recordings of the initial rate of release evoked by brief IHC Ca2+ -influx in an ex vivo cochlear preparation from hearing mice. We aimed to closely mimic physiological conditions by perforated-patch recordings from IHCs kept at the physiological resting potential and at body temperature...
December 5, 2023: Proceedings of the National Academy of Sciences of the United States of America
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