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Mitigating the functional deficit after neurotoxic motoneuronal loss by an inhibitor of mitochondrial fission
Ciuro M, Sangiorgio M, Cacciato V, Cantone G, Fichera C, Salvatorelli L, Magro G, Leanza G, Vecchio M, Valle MS, Gulino R (2024) Mitigating the functional deficit after neurotoxic motoneuronal loss by an inhibitor of mitochondrial fission. Int J Mol Sci 25(13):7059. doi: 10.3390/ijms25137059 PMID: 39000168
Objective: To use the Cholera Toxin B-Saporin (CTB-SAP) mouse animal model of Amyotrophic lateral sclerosis (ALS) to determine the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) for its potential neuroprotective effect.
Summary: Mdivi-1 reduced motor deficits in the ALS model. It also showed neuroprotective effects on motoneurons and promoted plasticity. This could represent a translational approach for motoneuron disorders.
Usage: To establish the model, mice received two injections of the retrogradely transported, ribosome-inactivating toxin, CTB-SAP (Cat. #IT-14) into the medial and lateral right gastrocnemius muscles, respectively, with a toxin dose of 6 μg/2 μL in PBS per injection.
Related Products: CTB-SAP (Cat. #IT-14)
A strength endurance exercise paradigm mitigates deficits in hypoglossal-tongue axis function, strength, and structure in a rodent model of hypoglossal motor neuron degeneration
Murphy ER, Thompson R, Osman KL, Haxton C, Brothers M, Lee L, Warncke K, Smith CL, Keilholz AN, Hamad A, Golzy M, Bunyak F, Ma L, Nichols NL, Lever TE (2022) A strength endurance exercise paradigm mitigates deficits in hypoglossal-tongue axis function, strength, and structure in a rodent model of hypoglossal motor neuron degeneration. Front Neurosci 16:869592. doi: 10.3389/fnins.2022.869592 PMID: 35844238
Objective: To investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure.
Summary: The tongue plays a crucial role in swallowing and impairment can lead to dysphagia, particularly in motor neuron diseases such as amyotrophic lateral sclerosis. This study utilized the authors previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted.
Usage: Rats received either a single “control” injection of unconjugated CTB + SAP (20μg CTB+25μg SAP) or CTB-SAP (Cat. #IT-14) injection (25μg of CTB conjugated to SAP) into the midline genioglossus muscle in the tongue base.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
How are adenosine and adenosine A2A receptors involved in the pathophysiology of amyotrophic lateral sclerosis?
Mori A, Cross B, Uchida S, Kerrick Walker J, Ristuccia R (2021) How are adenosine and adenosine A2A receptors involved in the pathophysiology of amyotrophic lateral sclerosis?. Biomedicines 9(8):1027. doi: 10.3390/biomedicines9081027
Objective: To examine potential biomarkers and the acute symptomatic pharmacology, including respiratory motor neuron control, of adenosine A2A receptor antagonism, and to explore the potential of the A2A receptor as a target for Amyotrophic Lateral Sclerosis (ALS) therapy.
Summary: CTB-SAP is listed in a table of experimental animal models of ALS. Intrapleural CTB-SAP injected rats (neurotoxic model of respiratory motor neuron death).
Related Products: CTB-SAP (Cat. #IT-14)
Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis.
McCall AL, Dhindsa JS, Pucci LA, Kahn AF, Fusco AF, Biswas DD, Strickland LM, Tseng HC, ElMallah MK (2020) Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis. Respir Physiol Neurobiol 282:103525. doi: 10.1016/j.resp.2020.103525
Summary: Tongue muscle weakness results in dysarthria and dysphagia leading to recurrent aspiration, choking, and aggravation of respiratory disease.
Related Products: CTB-SAP (Cat. #IT-14)
Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL-34, and SCF in amyotrophic lateral sclerosis
Trias E, Kovacs M, King PH, Si Y, Kwon Y, Varela V, Ibarburu S, Moura IC, Hermine O, Beckman JS, Barbeito L (2020) Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL-34, and SCF in amyotrophic lateral sclerosis. Glia 68(6):1165-1181. doi: 10.1002/glia.23768 PMID: 31859421
Objective: To investigate the pathogenic significance of denervated Schwann cells (SCs) accumulating following impaired axonal growth in amyotrophic lateral sclerosis (ALS).
Summary: There is strong evidence for a previously unknown inflammatory mechanism triggered by SCs in ALS peripheral nerves that has broad application in developing novel therapies.
Usage: Immunohistochemistry (1:250); AB-N01AP: NGFr (mu p75) Rabbit Polyclonal
Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)
Hypoglossal motor neuron death via intralingual CTB-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (ALS) related to dysphagia
Lind LA, Murphy ER, Lever TE, Nichols NL (2018) Hypoglossal motor neuron death via intralingual CTB-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (ALS) related to dysphagia. Neuroscience 390:303-316. doi: 10.1016/j.neuroscience.2018.08.026
Objective: Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to preserve swallowing function have seldom been studied in ALS models.
Summary: The authors report a novel experimental model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to study the impact of only hypoglossal motor neuron death without the many complications that are present in ALS models.
Usage: Hypoglossal motor neuron survival, swallowing function, and hypoglossal motor output were assessed in Sprague Dawley rats after intralingual injection of either CTB-SAP (25 ug) or unconjugated CTB and SAP (controls) into the genioglossus muscle.
Related Products: CTB-SAP (Cat. #IT-14)
Novel targets for modulation of plasticity in a mouse model of motoneuron degeneration.
Gulino R, Forte S, Parenti R, Gulisano M (2016) Novel targets for modulation of plasticity in a mouse model of motoneuron degeneration. Neuroscience 2016 Abstracts 812.14 / OO13. Society for Neuroscience, San Diego, CA.
Summary: A successful spinal cord repairing strategy should involve the activation of neural precursor cells. Unfortunately, their ability to generate neurons aſter injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Although considerable attention has been devoted to the toxic effects of the TDP-43 cytoplasmic aggregates, the functional role of this factor remains poorly investigated. Notably, TDP-43 is present in the dendrites where it behaves as a modulator of local RNA translation. Moreover, it is crucial for synaptic plasticity and locomotion in Drosophila. Here, we would like to deepen the investigation of this model of spinal plasticity. Aſter lesion, we observed a glial reaction and an activity-dependent modification of Synapsin-I, Shh, Noggin, Numb and TDP-43 proteins. Multivariate regression was used to model the possible association between these proteins, as well as with the motor performance. We found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb, thus suggesting that TDP-43 is likely an important regulator of synaptic plasticity. Given the well-known role of morphogens such as Shh, Noggin and Numb in neurogenesis and the above described functions of TDP-43, we believe that an in vivo manipulation of their signaling pathways after lesion could represent a putative method of improving regeneration and recovery by affecting synaptic plasticity and/or neurogenesis.
Related Products: CTB-SAP (Cat. #IT-14)
Neuroplasticity and repair in rodent neurotoxic models of spinal motoneuron disease.
Gulino R (2016) Neuroplasticity and repair in rodent neurotoxic models of spinal motoneuron disease. Neural Plast 2016:2769735. doi: 10.1155/2016/2769735
Summary: TDP-43 (Transactive response DNA-binding protein) is a highly conserved nuclear protein that binds both DNA and RNA. It has been found in cytoplasmic protein aggregates of patients with conditions such as amyotrophic lateral sclerosis and Alzheimer’s disease. In this work the authors examine the role of TDP-43 in spinal cord plasticity. Mice received bilateral 3-μg injections of CTB-SAP (Cat. #IT-14) into the lateral and medial gastrocnemius muscles. The results indicate that motor performance is dependent on expression of synapsin-I, which in turn may be dependent on TDP-43.
Related Products: CTB-SAP (Cat. #IT-14)
Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.
Nichols N, Vinit S, Bauernschmidt L, Mitchell G (2015) Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29. doi: 10.1016/j.expneurol.2014.11.011
Summary: Amyotrophic lateral sclerosis (ALS) ultimately causes death from ventilator failure. Genetic models of ALS suffer from high variability of the rate, timing, and extent of respiratory motor neuron death. The authors created a novel model of induced respiratory motor neuron death using CTB-SAP (Cat. #IT-14). Rats received 25 μg or 50 μg intrapleural injections of CTB-SAP; Saporin (Cat. #PR-01) was used as a control. After 7 days, motor neuron survival approximated what is seen in end-stage ALS rats, while there was minimal cell death in other brainstem or spinal cord regions. CTB-SAP also caused microglial activation, decreased breathing during chemoreceptor stimulation, and diminished phrenic motor output in anesthetized rats – all hallmarks of ALS.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis
Pehar M, Cassina P, Vargas MR, Castellanos R, Viera L, Beckman JS, Estévez AG, Barbeito L (2004) Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J Neurochem 89(2):464-473. doi: 10.1111/j.1471-4159.2004.02357.x PMID: 15056289
Summary: The role of p75-mediated activity evaluated with p75NTR blocking antibody. Motor neuron loss induced by reactive astrocytes was prevented by blocking the p75NTR.
Related Products: NGFr (mu p75) Rabbit Polyclonal (Cat. #AB-N01)