The Experts below are selected from a list of 108 Experts worldwide ranked by ideXlab platform
Petri Olivius - One of the best experts on this subject based on the ideXlab platform.
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β bungarotoxin application to the round window an in vivo deafferentation model of the inner ear
Hearing Research, 2010Co-Authors: Bjorn Palmgren, Zhe Jin, Yu Jiao, Petri OliviusAbstract:Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. Beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received Beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the Beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of Beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.
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Beta-Bungarotoxin application to the round window: an in vivo deafferentation model of the inner ear.
Hearing research, 2010Co-Authors: Bjorn Palmgren, Zhe Jin, Yu Jiao, Petri OliviusAbstract:Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. Beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received Beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the Beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of Beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.
J M Lindstrom - One of the best experts on this subject based on the ideXlab platform.
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Neurons of the chick brain and retina expressing both alpha-bungarotoxin-sensitive and alpha-bungarotoxin-insensitive nicotinic acetylcholine receptors: an immunohistochemical analysis.
Brain research, 1992Co-Authors: L R Britto, D E Hamassaki-britto, E S Ferro, K T Keyser, H J Karten, J M LindstromAbstract:Immunohistochemical methods were used to study the possible co-localization of two alpha-bungarotoxin-sensitive (alpha 7 and alpha 8) and two alpha-bungarotoxin-insensitive (beta 2 and alpha 3) subunits of the nicotinic acetylcholine receptors in neurons of the chick brain and retina. Several structures contained neurons that were doubly-labeled with antibodies against the alpha 7 subunit and the beta 2 subunit. These structures included, for example, the interpeduncular nucleus, nucleus spiriformis lateralis, optic tectum, pretectal visual nuclei, and the lateral hypothalamus. Double-labeling with antibodies against the alpha 7 and alpha 8 subunits was also seen in several regions, which included the interpeduncular nucleus, visual pretectum, lateral hypothalamus, dorsal thalamus, and the habenular complex. In the retina, many cells in the inner nuclear layer were observed to contain alpha 8 and alpha 3 subunits, whereas neurons in the ganglion cell layer were seen to contain alpha 7 and alpha 8 or, less frequently, alpha 7 and alpha 3 subunits. These results indicate that alpha-bungarotoxin-sensitive and alpha-bungarotoxin-insensitive subunits of the nicotinic receptors are co-expressed by neurons of the chick brain and retina.
Xingcai Liang - One of the best experts on this subject based on the ideXlab platform.
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A novel serine protease inhibitor from Bungarus fasciatus venom.
Peptides, 2007Co-Authors: Hailong Yang, Wei-kai Gao, Ren Lai, Jingze Liu, Xingcai LiangAbstract:By Sephadex G-50 gel filtration, cation-exchange CM-Sephadex C-25 chromatography and reversed phase high-performance liquid chromatography (HPLC), a novel serine protease inhibitor named bungaruskunin was purified and characterized from venom of Bungarus fasciatus. Its cDNA was also cloned from the cDNA library of B. fasciatus venomous glands. The predicted precursor is composed of 83 amino acid (aa) residues including a 24-aa signal peptide and a 59-aa mature bungaruskunin. Bungaruskunin showed maximal similarity (64%) with the predicted serine protease inhibitor blackelin deduced from the cDNA sequence of the red-bellied black snake Pseudechis porphyriacus. Bungaruskunin is a Kunitz protease inhibitor with a conserved Kunitz domain and could exert inhibitory activity against trypsin, chymotrypsin, and elastase. By screening the cDNA library, two new B chains of Beta-Bungarotoxin are also identified. The overall structures of bungaruskunin and Beta-Bungarotoxin B chains are similar; especially they have highly conserved signal peptide sequences. These findings strongly suggest that snake Kunitz/BPTI protease inhibitors and neurotoxic homologs may have originated from a common ancestor.
Ephraim Katchalskikatzir - One of the best experts on this subject based on the ideXlab platform.
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a beta hairpin structure in a 13 mer peptide that binds alpha bungarotoxin with high affinity and neutralizes its toxicity
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Tali Scherf, Roni Kasher, Moshe Balass, Mati Fridkin, Sara Fuchs, Ephraim KatchalskikatzirAbstract:Snake-venom alpha-bungarotoxin is a member of the alpha-neurotoxin family that binds with very high affinity to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. The structure of the complex between alpha-bungarotoxin and a 13-mer peptide (WRYYESSLEPYPD) that binds the toxin with high affinity, thus inhibiting its interactions with AChR with an IC(50) of 2 nM, has been solved by (1)H-NMR spectroscopy. The bound peptide folds into a beta-hairpin structure created by two antiparallel beta-strands, which combine with the already existing triple-stranded beta-sheet of the toxin to form a five-stranded intermolecular, antiparallel beta-sheet. Peptide residues Y3(P), E5(P), and L8(P) have the highest intermolecular contact area, indicating their importance in the binding of alpha-bungarotoxin; W1(P), R2(P), and Y4(P) also contribute significantly to the binding. A large number of characteristic hydrogen bonds and electrostatic and hydrophobic interactions are observed in the complex. The high-affinity peptide exhibits inhibitory potency that is better than any known peptide derived from AChR, and is equal to that of the whole alpha-subunit of AChR. The high degree of sequence similarity between the peptide and various types of AChRs implies that the binding mode found within the complex might possibly mimic the receptor binding to the toxin. The design of the high-affinity peptide was based on our previous findings: (i) the detection of a lead peptide (MRYYESSLKSYPD) that binds alpha-bungarotoxin, using a phage-display peptide library, (ii) the information about the three-dimensional structure of alpha-bungarotoxin/lead-peptide complex, and (iii) the amino acid sequence analysis of different AChRs.
Bjorn Palmgren - One of the best experts on this subject based on the ideXlab platform.
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β bungarotoxin application to the round window an in vivo deafferentation model of the inner ear
Hearing Research, 2010Co-Authors: Bjorn Palmgren, Zhe Jin, Yu Jiao, Petri OliviusAbstract:Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. Beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received Beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the Beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of Beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.
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Beta-Bungarotoxin application to the round window: an in vivo deafferentation model of the inner ear.
Hearing research, 2010Co-Authors: Bjorn Palmgren, Zhe Jin, Yu Jiao, Petri OliviusAbstract:Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. Beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received Beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the Beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of Beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.