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)

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).

See: Seven YB et al. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol 323:113067, 2020.

Related Products: CTB-SAP (Cat. #IT-14)

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.

See: Lind LA et al. 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, 2018.

Related Products: CTB-SAP (Cat. #IT-14)

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)

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)

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)

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)

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)

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)

Peterson WE, Jordan LM, Brownstone RM (2001) Immunolesioning of identified motoneuron pools following intramuscular injection of the immunotoxin, 192-IgG-saporin, in neonatal rats. Neuroscience 2001 Abstracts 626.14. Society for Neuroscience, San Diego, CA.

Summary: Studies have shown that the immunotoxin, 192-IgG-Saporin, can selectively lesion p75-positive cholinergic neurons of the basal forebrain in adult rats. Here we demonstrate the novel use of 192-IgG-Saporin to induce MN loss following intramuscular (I.M.) injection in neonatal rats. Two days following I.M. injection of 192-IgG-Cy3, neonatal rats (but not adult rats or neonatal mice) had Cy3-labeled MNs. This suggests that the 192-IgG antibody and its conjugates can be internalised by receptor-mediated endocytosis and retrogradely transported to spinal motor neurons. To induce MN loss, the left hind limb musculature of anaesthetised Sprague-Dawley rats were exposed, and several muscles injected with 0.5μg of 192-IgG-Saporin (Chemicon). Right hind-limb muscles were injected with DiI. Animals were sacrificed 25 days later. Ten μm coronal sections were obtained using a cryostat and Nissl stained. The neonatal rats showed signs of a locomotor deficit 2.5 weeks post injection with 192-IgG-Saporin, which increased slightly in severity over the next week and a half. Nissl stained coronal sections of the lumbar region showed an obvious MN deficit on the 192-IgG-Saporin treated side compared to control side. The injected muscles were also severely atrophic, a not unexpected finding given that they too express p75 receptors. We conclude that 192-IgG-Saporin can be used to lesion MN pools when IM injected in neonatal rats. This model may prove useful for testing cell replacement therapies for the treatment of MN diseases like amyotrophic lateral sclerosis (ALS).

Related Products: 192-IgG Mouse Monoclonal, Cy3-labeled (Cat. #AB-N43FL3)