Chew C, Sengelaub DR. Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle (2021) Dev Neurobiol 81(1):22-35. doi: 10.1002/dneu.22794
Objective: To determine where the necessary site of androgen action is for exercise-driven neuroprotective effects on induced dendritic atrophy.
Summary: Exercise following neural injury exerts a protective effect on motoneuron dendrites, which acts via androgen receptor action at the target muscle.
Dose: Motoneurons innervating the left vastus medialis (VM) muscle were selectively killed by intramuscular injection of cholera toxin-conjugated saporin (CTB-SAP).
Kim HN, Kim JY. A Systematic Review of Oropharyngeal Dysphagia Models in Rodents (2021) Int J Environ Res Public Health 18(9):4987. doi: 10.3390/ijerph18094987
Objective: To organize the rodent models of oropharyngeal dysphagia reported to date.
Summary: Applying and analyzing the treatment in rodent models of dysphagia induced from various causes is an essential process to develop symptom-specific treatments. The results of this study provide fundamental and important data for selecting appropriate animal models to study dysphagia.
Dose: CTB-SAP treated rats exhibited targeted hypoglossal motor neuron death; decreased hypoglossal motor output; and swallowing and lick deficits.
Lind LA, Lever TE, Nichols NL. Tongue and hypoglossal morphology after intralingual cholera toxin B-saporin injection (2021) Muscle Nerve 63(3):413-420. doi: 10.1002/mus.27131
Objective: To evaluate tongue morphology and ultrastructural changes in hypoglossal neurons and nerve fibers in an inducible rat model of dysphagia.
Summary: Preliminary results indicate this model may have translational application to a variety of neurodegenerative diseases resulting in tongue dysfunction and associated dysphagia.
Dose: Rats assigned to the CTB-SAP group (n = 10) received 25 μg CTB-SAP to produce hypoglossal motor neuron death.
Borkowski LF, Nichols NL. Differential mechanisms are required for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections. (2020) Exp Neurol 334:113460. doi: 10.1016/j.expneurol.2020.113460
Objective: To understand the mechanism responsible for this difference in magnitude of phrenic long-term facilitation (pLTF).
Summary: pLTF in 7d CTB-SAP treated rats is elicited primarily through TrkB and PI3K/Akt-dependent mechanisms, whereas BDNF and MEK/ERK-dependent mechanisms induce pLTF in 28d CTB-SAP treated rats.
Dose: Rats received bilateral intrapleural injections of CTB-SAP; 25 μg dissolved in PBS.
Chew C, Sengelaub DR. Exercise promotes recovery after motoneuron injury via hormonal mechanisms. (2020) Neural Regen Res 15(8):1373-1376. doi: 10.4103/1673-5374.274323
Objective: To describe how exercise is neuroprotective for motoneurons, accelerating axon regeneration following axotomy and attenuating dendritic atrophy following the death of neighboring motoneurons.
Summary: Exercise offers a simple, low barrier-to-entry behavioral intervention which is neuroprotective and pro-regenerative following neural injury.
Dose: Motoneurons innervating the left vastus medialis muscle were selectively killed by intramuscular injection of CTB-SAP (2 μL, 0.1%).
Fang J, Li L, Zhai H, Qin B, Quan D, Shi E, Zhu M, Yang J, Liu X, Gu L (2020) Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model. Neurochem Res 45(11):2800-2813. doi: 10.1007/s11064-020-03120-0
Summary: The authors refer to a review by Gulino describing two rodent models of motoneuron degeneration were induced by neurotoxics including volkensin and cholera toxin-B saporin, which are able to destroy motoneurons through retrograde transportation. (Gulino R. Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease. Neural Plast 2016:2769735. doi: 10.1155/2016/2769735)
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. The authors refer to work completed by Lind et al. (Lind, L.A., Murphy, E.R., Lever, T.E., Nichols, N.L., 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.)
Seven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. (2020) Exp Neurol 323:113067. doi: 10.1016/j.expneurol.2019.113067
Objective: To test the hypothesis that A2A receptor antagonism promotes phrenic motor neuron survival and preserves diaphragm function when faced with toxic, neurodegenerative insults that lead to phrenic motor neuron death.
Summary: The authors utilized a novel neurotoxic model of respiratory motor neuron death using intrapleural injections of CTB-SAP. A2A receptors contribute to neurotoxic phrenic motor neuron death, an effect mitigated by A2A receptor antagonism.
Dose: Intrapleural administration of CTB-SAP (25 μg per side) causes: 1) profound phrenic motor neuron death (~5% survival); 2) ~7-fold increase in phrenic motor neuron A2A receptor expression prior to cell death; and 3) diaphragm muscle paralysis (inactive in most rats; ~7% residual diaphragm EMG amplitude during room air breathing).
Borkowski LF, Nichols NL. A2A and 5‐HT Receptors are Differentially Required for Respiratory Plasticity Over the Course of Motor Neuron Loss in Intrapleurally CTB‐SAP Treated Rats. (2019) FASEB J 33: 843.3. doi: 10.1096/fasebj.2019.33.1_supplement.843.3
Objective: To investigate the role of serotonin (5-HT) and adenosine 2A (A2A) receptors in respiratory plasticity.
Summary: A2A receptors are necessary for respiratory plasticity early (7d), but 5-HT receptors are required late (28d).
Dose: Bilateral, intrapleural injections of: 1) CTB-SAP (25 μg), or 2) un-conjugated CTB and SAP (control) in rats.
Chew C, Sengelaub DR. Neuroprotective Effects of Exercise on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons. (2019) Neurorehabil Neural Repair 33(8):656-667. doi: 10.1177/1545968319860485
Objective: To explore whether exercise shows the same neuroprotective effect on induced dendritic atrophy as that seen with androgen treatment.
Summary: Exercise following neural injury exerts a protective effect on motoneuron dendrites comparable to that seen with exogenous androgen treatment.
Dose: Motoneurons innervating the left vastus medialis muscle were selectively killed by intramuscular injection of CTB-SAP (2 μL, 0.1%). Saporin injection reduced the weight of the vastus medialis muscle; exercise had no effect on muscle weight.
Gulino R, Vicario N, Giunta MAS, Spoto G, Calabrese G, Vecchio M, Gulisano M, Leanza G, Parenti R. Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss. (2019) Int J Mol Sci 20(6):1500. doi: 10.3390/ijms20061500
Objective: To use a neurotoxic model of spinal motoneuron depletion, induced by injection of CTB-SAP, to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord.
Summary: Plastic changes in surviving motoneurons produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be driven by glutamatergic signaling; astrocytes contacting surviving motoneurons may support this process.
Dose: Mice received 2 injections of CTB-SAP (3 mcg CTB-Sap in 2 mcL PBS) into the medial and lateral left gastrocnemius muscle.
Kiuchi MG, Chen S, Carnagarin R, Matthews VB, Schlaich MP. Renal denervation for treating congenital long QT syndrome: shortening the QT interval or modulating sympathetic tone? (2019) Europace 21(11):1755-1756. doi: 10.1093/europace/euz251
Summary: Targeted ablation of cardiac sympathetic neurons (TACSN) through CTB-SAP injection in the left stellate ganglion (LSG), inhibited its activation, improved sympathetic remodelling, and restored cardiac autonomic balance (see Xiong et al., 2018).
Sajjadi E, Seven YB, Simon AK, Zwick A, Satriotomo I, & Mitchell GS. Adenosine 2A Receptor Inhibition Promotes Neuroprotection Following Toxic Insult to Phrenic Motor Neurons. (2019) FASEB J 33: 844.3. doi: 10.1096/fasebj.2019.33.1_supplement.844.3
Objective: The authors explored the role of A2A receptors in phrenic motor neuron cell death in vivo.
Summary: A2A receptors, which contribute to motor neuron death during toxic insults, are upregulated in spared phrenic motor neurons of CTB-SAP treated rats. This is an important finding since A2A receptor upregulation may accelerate motor neuron death in neurodegenerative diseases like ALS.
Dose: CTB-SAP selectively killed nearly all phrenic motor neurons within a week and caused diaphragm paralysis (p<0.01).
Seven YB, Mitchell GS. Mechanisms of compensatory plasticity for respiratory motor neuron death. (2019) Respir Physiol Neurobiol 265:32-39. doi: 10.1016/j.resp.2019.01.001
Review: discusses recent advances in understanding of mechanisms giving rise to compensatory respiratory plasticity in response to respiratory motor neuron death.
Lind LA, Murphy ER, Lever TE, & Nichols NL. Hypoglossal motor neuron death via intralingual ctb-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (als) related to dysphagia. (2018). Neuroscience, 390 303-316. 2018/09/05. PMC6168367 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.
Dose: 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.
Nichols NL, Craig TA, Tanner MA. Phrenic long-term facilitation following intrapleural CTB-SAP-induced respiratory motor neuron death. (2018) Respir Physiol Neurobiol. 256:43-49. doi: 10.1016/j.resp.2017.08.003
Objective: To study the impact of respiratory motor neuron death.
Summary: Intrapleural CTB-SAP mimics aspects of ALS. Seven days of CTB-SAP enhances respiratory plasticity.
Dose: Bilateral intrapleural injections of: 1) CTB-SAP (25 μg), or 2) un-conjugated CTB and SAP (control).
Qiu M, Li J, Tan L, Zhang M, Zhou G, Zeng T, & Li A. Targeted Ablation of Distal Cerebrospinal Fluid-Contacting Nucleus Alleviates Renal Fibrosis in Chronic Kidney Disease. (2018) Front Physiol 9:1640. doi: 10.3389/fphys.2018.01640
Objective: To test the hypothesis that distal cerebrospinal fluid-contacting nucleus (dCSF-CNs) might affect the renin-angiotensin system (RAS) in kidney injury progression.
Summary: Less CTB-labeled neurons were found in dCSF-CNs of CTB-SAP-treated rats. Meanwhile, CTB-SAP downregulated AGT, Ang II, AT1R, NOX2, catalase, MCP-1, IL-6, fibronectin, and collagen I, and upregulated ACE2 and Mas receptor. Targeted dCSF-CNs ablation could alleviate renal inflammation and fibrosis in chronic kidney injury.
Dose: CTB-SAP (500 ng) into the lateral ventricles over a 3-min period.
Song SY, Zhang LC. The Establishment of a CSF-Contacting Nucleus “Knockout” Model Animal. (2018) Front Neuroanat 12:22. doi: 10.3389/fnana.2018.00022
Objective: To establish a cerebrospinal fluid (CSF)-contacting nucleus-deficient model animal using cholera toxin B subunit-saporin (CTB-SAP).
Summary: The complete ablation occurred by Day 7 after CTB-SAP microinjection. A model animal that had no CSF-contacting nucleus was established after survival beyond that time point. No obvious effects were observed in the vital status of the model animals, and their survival was ensured. The common physiological parameters of model animals were stable. The present study provides a method to establish a CSF-contacting nucleus “knockout” model animal, which is similar to a gene knockout model animal for studying this particular nucleus in vivo.
Dose: 3 μl (500 ng) CTB-SAP was microinjected into the lateral ventricle.
Xiong L, Liu Y, Zhou M, Wang G, Quan D, Shuai W, Shen C, Kong B, Huang C, & Huang H. Targeted Ablation of Cardiac Sympathetic Neurons Attenuates Adverse Post-Infarction Remodeling and Left Ventricle Dysfunction. (2018) Exp Physiol 103: 1221-1229. doi: 10.1113/EP086928
Objective: To determine whether targeted ablation of cardiac sympathetic neurons (TACSN) could suppress myocardial infarction-induced adverse cardiac remodeling and left ventricle dysfunction.
Summary: TACSN significantly alleviated sympathetic remodeling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis, and improved the left ventricular function. Thus, TACSN may have a beneficial effect on adverse post-infarction remodeling and left ventricle dysfunction.
Dose: 20 μl of CTB-SAP (1.2 mg/ml) was mixed with 4 μl of 3% Evans blue dye to make it visible (CTB-SAP is colorless), ensuring localization within the ganglia. The CTB-SAP/Evans blue dye solution was slowly and intermittently injected into the left stellate ganglia using a glass micropipette.
Xiong L, Liu Y, Zhou M, Wang G, Quan D, Shen C, Shuai W, Kong B, Huang C, Huang H. Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction. (2018) Europace 20(12):2036-2044. doi: 10.1093/europace/euy090
Objective: To evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI).
Summary: Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.
Dose: 20 μl of CTB-SAP (1.2 mg/ml) was mixed with 4 μl of 3% Evans blue dye to make it visible (CTB-SAP is colorless), ensuring localization within the ganglia. The CTB-SAP/ Evan blue dye solution was slowly and intermittently injected into the left stellate ganglia using a glass micropipette.
Cai Y, Chew C, Muñoz F, Sengelaub DR. (2017) Neuroprotective Effects of Testosterone Metabolites and Dependency on Receptor Action on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons. Dev Neurobiol 77(6):691-707. PMID: 27569375 (Targeting Trends 17q1)
Gulino R, Parenti R, Gulisano M. (2017) Sonic Hedgehog and Tdp-43 Participate in the Spontaneous Locomotor Recovery in a Mouse Model of Spinal Motoneuron Disease. J Funct Morphol Kinesiol 2:11. (read summary)
Fei Y, Wang X, Chen S, Zhou Q, Zhang C, Li Y, Sun L, Zhang L. (2016) Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus. Neurochem Res 41(7):1651-1661. PMID: 26961890 (Targeting Trends 16q3)
Gulino R. (2016) Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease. Neural Plast 2016:2769735. PMID: 26862439 (Targeting Trends 16q2)
Gulino R, Forte S, Parenti R, Gulisano M (2016) Novel targets for modulation of plasticity in a mouse model of motoneuron degeneration. Soc Neurosci Meeting Abstract 812.14
Xia W, Liu Y. (2016) Targeted Ablation of Cardiac Sympathetic Neurons: A Promising Approach to Prevent Sudden Cardiac Death. Int J Cardiol 202:425-26. PMID: 26433164 (Targeting Trends 17q1)
Gulino R, Parenti R, Gulisano M. (2015) Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease. Biomed Res Int 2015:654637. (Targeting Trends 15q3)
Nichols NL, Vinit S, Bauernschmidt L, Mitchell GS. (2015) Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29 (Targeting Trends 15q1)
Xing D, Wu Y, Li G, Song S, Liu Y, Liu H, Wang X, Fei Y, Zhang C, Li Y, Zhang L. (2015) Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite. Physiol Behav 147:291-299. (Targeting Trends 15q3)
Wu YH, Song SY, Liu H, Xing D, Wang X, Fei Y, Li GL, Zhang C, Li Y, Zhang LC. (2015) Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress. Neuropeptides 51:43-54. (Targeting Trends 15q3)
Cao J WT, Zhang LC. (2014) Targeted damage of the cerebrospinal fluid-contacting nucleus contributes to the pain behavior and the expression of 5-HT and c-Fos in the spinal dorsal horn of rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 30(3):218-222. (Targeting Trends 14q4)
Liu H, Yan WW, Lu XX, Zhang XL, Wei JQ, Wang XY, Wang T, Wu T, Cao J, Shao CJ, Zhou F, Zhang HX, Zhang P, Zang T, Lu XF, Cao JL, Ding HL, Zhang LC. (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261C:475-485. (Targeting Trends 14q4)
Gulino R, Gulisano M. (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1-2):102-109. (Targeting Trends 13q4)
Gulino R, Gulisano M. (2012) Involvement of brain-derived neurotrophic factor and sonic hedgehog in the spinal cord plasticity after neurotoxic partial removal of lumbar motoneurons. Neurosci Res 73(3):238-247. (Targeting Trends 12q3)
Cerminara NL (2010) Cerebellar modules: individual or composite entities? J Neurosci 30(48):16065-16067. (Targeting Trends 11q1)
Gulino R, Perciavalle V, Gulisano M (2010) Expression of cell fate determinants and plastic changes after neurotoxic lesion of adult mice spinal cord by cholera toxin-B saporin. Eur J Neurosci 31(8):1423-1434. (Targeting Trends 10q3)
Gulino R, Perciavalle V, Gulisan M. (2010) Role of Cell Fate Determinants in a Model of Spinal Cord Neurotoxic Lesion Induced by Cholera Toxin B-Saporin. Targeting Trends 11(3).
Lujan HL, DiCarlo SE. (2010) Targeted Ablation of Sympathetic Neurons Reduces Ventricular Arrhythmias and Autonomic Dysreflexia. Targeting Trends 11(4).
Lujan HL, Palani G, Peduzzi J, Dicarlo SE (2010) Targeted Ablation of Mesenteric Projecting Sympathetic Neurons Reduces the Hemodynamic Response to Pain in Conscious Spinal Cord Transected Rats. Am J Physiol Regul Integr Comp Physiol 298(5):R1358-1365. (Targeting Trends 10q3)
Lujan HL, Palani G, Zhang L, Dicarlo SE (2010) Targeted Ablation of Cardiac Sympathetic Neurons Reduces the Susceptibility to Ischemia-Induced Sustained Ventricular Tachycardia in Conscious Rats. Am J Physiol Heart Circ Physiol 298:H1330-H1339. (Targeting Trends 10q2)
See also: Society for Neuroscience 2010 Abstracts
Fargo KN, Foster AM, Sengelaub DR (2009) Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons. Dev Neurobiol 69:825-835. (Targeting Trends 09q4)
Little CM, Coons KD, Sengelaub DR (2009) Neuroprotective effects of testosterone on the morphology and function of somatic motoneurons following the death of neighboring motoneurons. J Comp Neurol 512:359-372. (Targeting Trends 09q2)
Lujan HL, Palani G, Chen Y, Peduzzi JD, Dicarlo SE (2009) Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats. Am J Physiol Heart Circ Physiol 296:H1305-1311. (Targeting Trends 09q3)
Wilson RE, Coons KD, Sengelaub DR (2009) Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: efficacy in female rats. Neurosci Lett 465:123-127. (Targeting Trends 10q1)
See also: Society for Neuroscience 2009 Abstracts
Pijpers A, Winkelman BH, Bronsing R, Ruigrok TJ (2008) Selective impairment of the cerebellar C1 module involved in rat hind limb control reduces step-dependent modulation of cutaneous reflexes. J Neurosci 28:2179-2189. (Targeting Trends 08q2)
See also: Society for Neuroscience 2008 Abstracts
Wu M, Kc P, Mack SO, Haxhiu MA (2006) Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea affects ventilatory responses to hypercapnia and hypoxia. Respir Physiol Neurobiol 152(1):36-50. (Targeting Trends 05q4)
See also: Society for Neuroscience 2006 Abstracts
Lappi DA (2005) Targeted Toxins from Here to There. Targeting Trends 6(3):1, 6.
Fargo KN, Sengelaub DR (2004) Testosterone manipulation protects motoneurons from dendritic atrophy after contralateral motoneuron depletion. J Comp Neurol 469(1):96-106. (Targeting Trends 04q2)
Fargo KN, Sengelaub DR (2004) Exogenous testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion. J Neurobiol 60(3):348-359. (Targeting Trends 05q1)(Targeting Trends 05q1)
See also: Society for Neuroscience 2004 Abstracts
Farhadi HF, Lepage P, Forghani R, Friedman HC, Orfali W, Jasmin L, Miller W, Hudson TJ, Peterson AC (2003) A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes. J Neurosci 23(32):10214-10223. (Targeting Trends 04q1)
Jasmin L, Janni G, Moallem TM, Lappi DA, Ohara PT (2000) Schwann cells are removed from the spinal cord after effecting recovery from paraplegia. J Neurosci 20(24):9215-9223.
Llewellyn-Smith IJ, Martin CL, Arnolda LF, Minson JB. Tracer-toxins: cholera toxin B-saporin as a model. (2000) J Neurosci Methods 103(1):83-90. doi: 10.1016/s0165-0270(00)00298-3. PMID: 11074098.
Llewellyn-Smith IJ, Martin CL, Arnolda LF, Minson JB. Retrogradely transported CTB-saporin kills sympathetic preganglionic neurons. (1999) Neuroreport 10(2):307-312. doi: 10.1097/00001756-199902050-00019