Limited proteolysis of single-chain tetanus toxin by tissue enzymes, in cultured brain tissue and during retrograde axonal to the spinal cord

1991 ◽  
Vol 343 (3) ◽  
Author(s):  
E. Habermann ◽  
U. Weller ◽  
M. Hudel
Keyword(s):  
Spinal Cord ◽  
Brain Tissue ◽  
Tetanus Toxin ◽  
Limited Proteolysis ◽  
Single Chain

scholarly journals Limited proteolysis of tetanus toxin. Relation to activity and identification of cleavage sites

1991 ◽  
Vol 202 (1) ◽  
pp. 48-51
Author(s):  
Kerstin G. KRIEGLSTEIN ◽  
Agnes H. HENSCHEN ◽  
Ulrich WELLER ◽  
Ernst HABERMANN
Keyword(s):  
Tetanus Toxin ◽  
Limited Proteolysis ◽  
Cleavage Sites

scholarly journals Development of the central nervous system in guinea pig (Cavia porcellus, Rodentia, Caviidae)

2016 ◽  
Vol 36 (8) ◽  
pp. 753-760 ◽  
Author(s):  
Fernanda Menezes de Oliveira e Silva ◽  
Dayane Alcantara ◽  
Rafael Cardoso Carvalho ◽  
Phelipe Oliveira Favaron ◽  
Amilton Cesar dos Santos ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Guinea Pig ◽  
Brain Tissue ◽  
Light And Electron Microscopy ◽  
Cauda Equina ◽  
Neural Tube Closure ◽  
Morphological Studies ◽  
The Central Nervous System

Abstract: This study describes the development of the central nervous system in guinea pigs from 12th day post conception (dpc) until birth. Totally, 41 embryos and fetuses were analyzed macroscopically and by means of light and electron microscopy. The neural tube closure was observed at day 14 and the development of the spinal cord and differentiation of the primitive central nervous system vesicles was on 20th dpc. Histologically, undifferentiated brain tissue was observed as a mass of mesenchymal tissue between 18th and 20th dpc, and at 25th dpc the tissue within the medullary canal had higher density. On day 30 the brain tissue was differentiated on day 30 and the spinal cord filling throughout the spinal canal, period from which it was possible to observe cerebral and cerebellar stratums. At day 45 intumescences were visualized and cerebral hemispheres were divided, with a clear division between white and gray matter in brain and cerebellum. Median sulcus of the dorsal spinal cord and the cauda equina were only evident on day 50. There were no significant structural differences in fetuses of 50 and 60 dpc, and animals at term were all lissencephalic. In conclusion, morphological studies of the nervous system in guinea pig can provide important information for clinical studies in humans, due to its high degree of neurological maturity in relation to its short gestation period, what can provide a good tool for neurological studies.

scholarly journals A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

2015 ◽  
Vol 83 (7) ◽  
pp. 2714-2724 ◽  
Author(s):  
Madison Zuverink ◽  
Chen Chen ◽  
Amanda Przedpelski ◽  
Faith C. Blum ◽  
Joseph T. Barbieri
Keyword(s):  
Motor Neurons ◽  
Disulfide Bond ◽  
Light Chain ◽  
Tetanus Toxin ◽  
Thioredoxin Reductase ◽  
Single Chain ◽  
Intact Cells ◽  
Spastic Paralysis ◽  
Interchain Disulfide Bond ◽  
N Terminus

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT) are the most potent toxins for humans and elicit unique pathologies due to their ability to traffic within motor neurons. BoNTs act locally within motor neurons to elicit flaccid paralysis, while retrograde TeNT traffics to inhibitory neurons within the central nervous system (CNS) to elicit spastic paralysis. BoNT and TeNT are dichain proteins linked by an interchain disulfide bond comprised of an N-terminal catalytic light chain (LC) and a C-terminal heavy chain (HC) that encodes an LC translocation domain (HCT) and a receptor-binding domain (HCR). LC translocation is the least understood property of toxin action, but it involves low pH, proteolysis, and an intact interchain disulfide bridge. Recently, Pirazzini et al. (FEBS Lett 587:150–155, 2013,http://dx.doi.org/10.1016/j.febslet.2012.11.007) observed that inhibitors of thioredoxin reductase (TrxR) blocked TeNT and BoNT action in cerebellar granular neurons. In the current study, an atoxic TeNT LC translocation reporter was engineered by fusing β-lactamase to the N terminus of TeNT [βlac-TeNT(RY)] to investigate LC translocation in primary cortical neurons and Neuro-2a cells. βlac-TeNT(RY) retained the interchain disulfide bond, showed ganglioside-dependent binding to neurons, required acidification to promote βlac translocation, and was sensitive to auranofin, an inhibitor of thioredoxin reductase. Mutation of βlac-TeNT(RY) at C439S and C467S eliminated the interchain disulfide bond and inhibited βlac translocation. These data support the requirement of an intact interchain disulfide for LC translocation and imply that disulfide reduction is a prerequisite for LC delivery into the host cytosol. The data also support a model that LC translocation proceeds from the C to the N terminus. βlac-TeNT(RY) is the first reporter system to measure translocation by an AB single-chain toxin in intact cells.

scholarly journals THE LOCALIZED ACTION ON THE SPINAL CORD OF INTRAMUSCULARLY INJECTED TETANUS TOXIN

1942 ◽  
Vol 75 (5) ◽  
pp. 465-480 ◽  
Author(s):  
George H. Acheson ◽  
Oscar D. Ratnoff ◽  
Emanuel B. Schoenbach
Keyword(s):  
Spinal Cord ◽  
Tetanus Toxin ◽  
Peripheral Nerves ◽  
Mechanical Response ◽  
Motor Nerve ◽  
Single Stimulus ◽  
Altered State ◽  
Local Tetanus ◽  
Reflex Arc ◽  
Motor Nerves

Local tetanus limited to one leg was studied in cats after intramuscular injection of tetanus toxin. 1. The electric and mechanical response of the affected muscle after a single stimulus to the intact sensory-motor nerve is greater in amplitude and duration than the response of the corresponding muscle of the unaffected leg (Fig. 1). 2. This augmented response of the muscle is associated with an augmented response arising from the ipsilateral portion of the spinal cord, while the contralateral part of the cord is unaffected, as demonstrated by electrographic records from the motor nerves (Figs. 2 to 5). 3. The augmented muscular response is abolished when the reflex arc is broken, but the augmented response in the spinal cord is independent of changes in the muscle, the neuromuscular junction, the afferent and efferent peripheral nerves, and the dorsal root ganglia. 4. The augmented spinal response develops in the absence of the peripheral signs of local tetanus. Hence the pathogenesis of the altered state in the spinal cord is independent of the peripheral effects of the toxin. 5. In local tetanus, therefore, the toxin injected intramuscularly acts selectively upon the segments of the spinal cord which supply the innervation of the injected area. 6. The augmented spinal response may be prevented by section of the nerve trunks supplying the area of injection prior to the injection of the toxin. 7. It is concluded that in local tetanus the toxin is carried to the spinal cord by way of peripheral nerves.

C-terminal domain of tetanus toxin changes the apoptosis- and autophagy-related protein levels following spinal cord injury in rat brain

2017 ◽  
Vol 108 ◽  
pp. S89
Author(s):  
Murat Celal Sözbilen ◽  
Murat Öztürk ◽  
Gizem Kaftan ◽  
Taner Dağcı ◽  
Halit Özyalçın ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Brain ◽  
Tetanus Toxin ◽  
Related Protein ◽  
Protein Levels ◽  
Terminal Domain ◽  
Cord Injury

Tetanus Toxin in Dissociated Spinal Cord Cultures: Long-Term Characterization of Form and Action

2006 ◽  
Vol 47 (3) ◽  
pp. 930-937 ◽  
Author(s):  
William H. Habig ◽  
Hans Bigalke ◽  
Gregory K. Bergey ◽  
Elaine A. Neale ◽  
M. Carolyn Hardegree ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Tetanus Toxin

scholarly journals Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

2019 ◽  
Author(s):  
Christine Smothers ◽  
Chris Winkelman ◽  
Grant C. O’Connell
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Brain Injury ◽  
Brain Tissue ◽  
Tissue Sample ◽  
Surrogate Marker ◽  
Final Analysis ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Original Analysis

AbstractBackgroundDetection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care.MethodsPublically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls.ResultsThe top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart.ConclusionsThe five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.A FINAL PEER REVIEWED VERSION OF THIS ARTICLE HAS BEEN PUBLISHED IN BRAIN INJURY AT THE FOLLOWING DOI: 10.1080/02699052.2020.1764102There are some notable differences between the analysis presented in this preprint and our final peer-reviewed article. There was a single tissue sample originating from spinal cord that we had classified as a non-brain tissue in our original analysis outlined in this preprint. Because the composition of spinal cord and brain are highly similar in terms of gene expression, classifying this sample as a non-brain tissue dramatically reduced the levels of brain enrichment observed in the analysis. Because brain and spinal cord are molecularly highly similar, but technically distinct anatomical structures, we simply decided to exclude this sample from our final analysis published in Brain Injury to avoid confounds. The top 5 miRNAs identified in our original analysis still fell within the top 7 of this final analysis. In addition, the final analysis identified two additional miRNAs which could be candidate biomarkers based on levels of brain enrichment.The final article published in Brain Injury also reports an additional confirmatory tissue specificity analysis performed in a second independent dataset, as well as additional analysis examining the brain specificity of several notable previously proposed miRNA TBI biomarkers, which is not described in this preprint.

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