scholarly journals Macrophages Are Dispensable for Postnatal Pruning of the Cochlear Ribbon Synapses

2021 ◽  
Vol 15 ◽  
Author(s):  
Chaorong Yu ◽  
Hui-Ming Gao ◽  
Guoqiang Wan
Keyword(s):  
Hair Cells ◽  
Cochlear Hair Cells ◽  
Ribbon Synapses ◽  
The Central Nervous System ◽  
Complement Receptor 3 ◽  
Auditory Functions ◽  
The Complement System ◽  
The Brain ◽  
Synaptic Pruning ◽  
Genetic Mouse Models

Ribbon synapses of cochlear hair cells undergo pruning and maturation before the hearing onset. In the central nervous system (CNS), synaptic pruning was mediated by microglia, the brain-resident macrophages, via activation of the complement system. Whether a similar mechanism regulates ribbon synapse pruning is currently unknown. In this study, we report that the densities of cochlear macrophages surrounding hair cells were highest at around P8, corresponding well to the completion of ribbon synaptic pruning by P8–P9. Surprisingly, using multiple genetic mouse models, we found that postnatal pruning of the ribbon synapses and auditory functions were unaffected by the knockout of the complement receptor 3 (CR3) or by ablations of macrophages expressing either LysM or Cx3cr1. Our results suggest that unlike microglia in the CNS, macrophages in the cochlea do not mediate pruning of the cochlear ribbon synapses.

scholarly journals Expression and distribution of synaptotagmin isoforms in the zebrafish retina

2020 ◽  
Author(s):  
Diane Henry ◽  
Christina Joselevitch ◽  
Gary G. Matthews ◽  
Lonnie P. Wollmuth
Keyword(s):  
Amino Acid ◽  
Large Family ◽  
Amino Acid Residues ◽  
Ribbon Synapses ◽  
The Family ◽  
Class 1 ◽  
The Central Nervous System ◽  
Asynchronous Release ◽  
The Brain

ABSTRACTSynaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR and in situ hybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafish syt1, syt2, syt5 and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ dependent processes in different types of retinal neurons.

scholarly journals C3c intrathecal synthesis evaluation in patients with multiple sclerosis

2007 ◽  
Vol 65 (3b) ◽  
pp. 800-802 ◽  
Author(s):  
Bárbara Padilla-Docal ◽  
Alberto J Dorta-Contreras ◽  
Hermes Fundora-Hernández ◽  
Elena Noris-García ◽  
Raisa Bu-Coifiu-Fanego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Complement System ◽  
Progressive Disease ◽  
Degradation Process ◽  
Intrathecal Synthesis ◽  
Brain White Matter ◽  
The Central Nervous System ◽  
The Moment ◽  
The Complement System ◽  
The Brain

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). OBJECTIVE: To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction. METHOD: Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates. RESULTS: High values over 80% of intrathecal synthesis were obtained except in one of the patients. CONCLUSION: Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

scholarly journals Specific Influences of Early Acoustic Environments on Cochlear Hair Cells in Postnatal Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Aoshuang Chang ◽  
Peng Chen ◽  
Shasha Guo ◽  
Nana Xu ◽  
Wenlu Pan ◽  
...  
Keyword(s):  
Hair Cells ◽  
Acoustic Stimulation ◽  
Outer Hair Cells ◽  
Mature Stage ◽  
Cochlear Hair Cells ◽  
Acoustic Environment ◽  
Postnatal Maturation ◽  
Ribbon Synapses ◽  
Brainstem Response ◽  
Acoustic Environments

The auditory function develops and matures after birth in many mammalian species. After hearing onset, environmental sounds exert profound and long-term effects on auditory functions. However, the effects of the acoustic environment on the functional development of the peripheral auditory system, especially the cochlear sensory hair cells, are still unclear. In the present study, we exposed mouse pups to frequency-enriched acoustic environments in postnatal days 0–14. The results indicated that the acoustic environment significantly decreased the threshold of the auditory brainstem response in a frequency-specific manner. Compared with controls, no difference was found in the number and alignment of inner and outer hair cells or in the length of hair bundles after acoustic overstimulation. The expression and function of prestin, the motor protein of outer hair cells (OHCs), were specifically increased in OHCs activated by acoustic stimulation at postnatal days 7–11. We analyzed the postnatal maturation of ribbon synapses in the hair cell areas. After acoustic stimulation, the number of ribbon synapses was closer to the mature stage than to the controls. Taken together, these data indicate that early acoustic exposure could promote the functional maturation of cochlear hair cells and the development of hearing.

scholarly journals Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 112
Author(s):  
Sang-Yeon Lee ◽  
Jae Joon Han ◽  
Sang-Youp Lee ◽  
Gaon Jung ◽  
Hyun Jin Min ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
White Noise ◽  
Hair Cells ◽  
Murine Model ◽  
Outer Hair Cells ◽  
Saline Control ◽  
Noise Induced Hearing Loss ◽  
Cochlear Hair Cells ◽  
Ribbon Synapses

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.

scholarly journals The Kinocilia of Cochlear Hair Cells: Structures, Functions, and Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Difei Wang ◽  
Jun Zhou
Keyword(s):  
Auditory System ◽  
Hair Cells ◽  
Primary Cilia ◽  
Structure And Function ◽  
Biochemical Reactions ◽  
Cochlear Hair Cells ◽  
Evolutionarily Conserved ◽  
Genes Encoding ◽  
And Function ◽  
The Brain

Primary cilia are evolutionarily conserved and highly specialized organelles that protrude from cell membranes. Mutations in genes encoding ciliary proteins can cause structural and functional ciliary defects and consequently multiple diseases, collectively termed ciliopathies. The mammalian auditory system is responsible for perceiving external sound stimuli that are ultimately processed in the brain through a series of physical and biochemical reactions. Here we review the structure and function of the specialized primary cilia of hair cells, termed kinocilia, found in the mammalian auditory system. We also discuss areas that might prove amenable for therapeutic management of auditory ciliopathies.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Fluorocitrate Neural Dystrophy of the Guinea Pig Cochlea

1975 ◽  
Vol 33 ◽  
pp. 368-369
Author(s):  
G.J. Spector ◽  
C.D. Carr ◽  
I. Kaufman Arenberg ◽  
R.H. Maisel
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Sodium Phosphate ◽  
Sensory Cells ◽  
Barium Salt ◽  
Perfusion Medium ◽  
Cochlear Hair Cells ◽  
Neural Degeneration ◽  
Sodium Phosphate Buffer ◽  
Cochlear Neurons

All studies on primary neural degeneration in the cochlea have evaluated the end stages of degeneration or the indiscriminate destruction of both sensory cells and cochlear neurons. We have developed a model which selectively simulates the dystrophic changes denoting cochlear neural degeneration while sparing the cochlear hair cells. Such a model can be used to define more precisely the mechanism of presbycusis or the hearing loss in aging man.Twenty-two pigmented guinea pigs (200-250 gm) were perfused by the perilymphatic route as live preparations using fluorocitrate in various concentrations (15-250 ug/cc) and at different incubation times (5-150 minutes). The barium salt of DL fluorocitrate, (C6H4O7F)2Ba3, was reacted with 1.0N sulfuric acid to precipitate the barium as a sulfate. The perfusion medium was prepared, just prior to use, as follows: sodium phosphate buffer 0.2M, pH 7.4 = 9cc; fluorocitrate = 15-200 mg/cc; and sucrose = 0.2M.

Ultrastructural morphology of neurosecretory neurons in the barnacle Balanus amphitrite

1990 ◽  
Vol 48 (3) ◽  
pp. 434-435
Author(s):  
Grazia Tagliafierro ◽  
Cristiana Crosa ◽  
Marco Canepa ◽  
Tiziano Zanin
Keyword(s):  
Nervous System ◽  
Ultrastructural Level ◽  
Uranyl Acetate ◽  
Balanus Amphitrite ◽  
Neurosecretory Neurons ◽  
The Central Nervous System ◽  
Ultrathin Sections ◽  
Dense Core Granules ◽  
The Brain ◽  
Ocellar Nerve

Barnacles are very specialized Crustacea, with strongly reduced head and abdomen. Their nervous system is rather simple: the brain or supra-oesophageal ganglion (SG) is a small bilobed structure and the toracic ganglia are fused into a single ventral mass, the suboesophageal ganglion (VG). Neurosecretion was shown in barnacle nervous system by histochemical methods and numerous putative hormonal substances were extracted and tested. Recently six different types of dense-core granules were visualized in the median ocellar nerve of Balanus hameri and serotonin and FMRF-amide like substances were immunocytochemically detected in the nervous system of Balanus amphitrite. The aim of the present work is to localize and characterize at ultrastructural level, neurosecretory neuron cell bodies in the VG of Balanus amphitrite.Specimens of Balanus amphitrite were collected in the port of Genova. The central nervous system were Karnovsky fixed, osmium postfixed, ethanol dehydrated and Durcupan ACM embedded. Ultrathin sections were stained with uranyl acetate and lead citrate. Ultrastructural observations were made on a Philips M 202 and Zeiss 109 T electron microscopy.

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