targeted-toxins

Islam S, Gleber-Netto FO, Mulcahy CF, Glaun MDE, Srivastava S, Hunt PJ, Williams MD, Barbon CE, Spiotto M, Zhao W, Adebayo A, Akhter S, Xie T, Debnath KC, Sathishkumar HN, Myers B, Lothumalla S, Yama I, Burks JK, Gomez J, Rao X, Wang J, Woodman K, Mansour J, Arenkiel B, Osman KL, Haxton C, Lever TE, Hutcheson KA, Amit M (2024) Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma. Sco Transl Med 16:eabq5585. doi: 10.1126/scitranslmed.abq558

Objective: To understand the correlation between neuronal changes and patient-reported and functional outcomes in patients with oropharyngeal squamous cell carcinoma (OPSCC).

Summary: Tumor enrichment of adrenergic (TH+) and CGRP+ sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. The results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC.

Usage: 500 μg in 3 μl of alpha-CGRP-streptavidin-saporin (CGRP-SAP; #IT-94) and anti-ChAT-SAP (#IT-42) was stereotactically injected into the intraganglionic region over 3 min.

Related Products: CGRP-SAP (Cat. #IT-94), Anti-ChAT-SAP (Cat. #IT-42)

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)

Edwards CM, Guerrero IE, Thompson D, Dolezel T, Rinaman L (2024) An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. bioRxiv 2024.04.09.588717. doi: 10.1101/2024.04.09.588717 PMID: 38645069

Objective: To investigate the role of a gut vagal afferent-to-central noradrenergic pathway in modulating the retrieval of conditioned passive avoidance memory in rats.

Summary: This study explores how visceral sensory feedback via vagal afferents and central noradrenergic neurons influences passive avoidance memory retrieval. By lesioning specific neural pathways in adult male rats, the researchers demonstrate that disruption of these circuits significantly increased conditioned passive avoidance behavior, suggesting a critical role for these pathways in integrating interoceptive signals with contextual cues to modulate learned avoidance behaviors.

Usage: 250 ng of CCK-SAP (IT-31) was bilaterally injected into the nodose ganglion to selectively lesion gastrointestinal vagal afferents. 80 ng of Anti-DBH-SAP (IT-03) was injected bilaterally into the ventrolateral bed nucleus of the stria terminalis (vlBNST) to selectively lesion noradrenergic inputs to the anterior vlBNST.

Related Products: CCK-SAP (Cat. #IT-31), Anti-DBH-SAP (Cat. #IT-03)

Kumbhare D, Rajagopal M, Toms J, Freelin A, Weistroffer G, McComb N, Karnam S, Azghadi A, Murnane KS, Baron MS, Holloway KL (2024) Deep brain stimulation of nucleus basalis of meynert improves learning in rat model of dementia. bioRxiv 2024.04.05.588271. doi: 10.1101/2024.04.05.588271 PMID: 38645266

Objective: To assess the effects of varying stimulation patterns and duration on learning in a dementia rat model.

Summary: Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) has been considered a potential treatment for dementia, but more study is needed to determine the ideal parameters for NBM stimulation. 192-IgG-SAP (Cat. IT-01) was used to lesion cholinergic neurons of rats creating a rat model of dementia upon which NBM deep brain stimulation could be tested. The desired destruction of neurons was 70-80% cholinergic population lesioned, which through a panel of concentrations was determined to be a 0.50 μg dose. The rat models of dementia were then tested for ideal type and duration of deep brain stimulation to improve operant learning test performance.

Usage: 192-IgG-SAP was bilaterally injected in the NBM in the following amounts: 0.00 (control), 0.15, 0.30, 0.50, and 0.75 μg in 0.5 μl PBS.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Choi PP, Wang Q, Brenner LA, Li AJ, Ritter RC, Appleyard SM (2024) Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding. Endocrinology 165(5):bqae021. doi: 10.1210/endocr/bqae021 PMID: 38368624

Objective: To explore the role of NPY receptor-expressing neurons in regulating feeding behavior in rats.

Summary: In response to glucose deficits, rats exhibit counter-regulatory mechanisms to stimulate feeding. To clarify the role of NPY-sensitive neurons, these neurons were selectively ablated using NPY-SAP. The results showed that while Saporin-lesioned rats exhibited reduced 2DG-induced feeding, there was no impact on 2DG-induced locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release.

Usage: NPY-SAP [IT-28] or Blank-SAP [IT-21] (50 ng per 100nL/site) was used to specifically lesion NPY receptor-expressing neurons in the perifornical lateral hypothalamus of male rats.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement. bioRxiv 2024.03.07.583670. doi: 10.1101/2024.03.07.583670

Objective: Investigate the neuroprotective effect of treatment with the CB1 cannabinoid agonist, WIN55,212-2, against cholinergic degeneration.

Summary: The endocannabinoid (eCB) system plays a role in modulating learning and memory processes controlled by cholinergic neurotransmission. The authors propose that activation of this system is neuroprotective against cholinergic degeneration, such as what occurs in Alzheimer’s disease (AD). In a 192-IgG-SAP (Cat. IT-01) induced model of AD, a restoration of memory and learning was observed when rats were administered the CB1 cannabinoid agonist, WIN55,212-2.

Usage: Rats received injections of 192-IgG-saporin (130 ng/µl) into the nucleus basalis magnocellularis.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Luna-Munguia H, Gasca-Martinez D, Garay-Cortes A, Coutiño D, Regalado M, de Los Rios E, Villaseñor P, Hidalgo-Flores F, Flores-Guapo K, Benito BY, Concha L (2024) Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus. Mol Neurobiol 61(10):1-21. doi: 10.1007/s12035-024-04069-9 PMID: 38443731

Objective: To evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.

Summary: Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Regarding the pilocarpine-induced status epilepticus, an increased mortality rate was observed. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Usage: Injection of 192-IgG-SAP (375 ng/μl dissolved in sterile 0.1X PBS) and GAT1-SAP (325 ng/μl dissolved in sterile 0.1X PBS) into the MS to selectively target choline neuron or GABA populations of the medial septum, respectively.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)

Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287. doi: 10.1093/biolre/ioad147 PMID: 37930247

Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.

Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.

Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Björklund A, Barker RA (2024) The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease. Brain awae026. doi: 10.1093/brain/awae026 PMID: 38279949

Objective: Review the use of cholinergic cell replacement as a potential therapeutic strategy in Parkinson’s Disease (PD) and how rodent models of PD-like cognitive decline can be used by analyzing rodent and primate studies.

Summary: Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the Basal Forebrain system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

Usage: Rats were given 192-IgG-SAP (IT-01), 0.2-0.4 μg, delivered as a single 0.3-1.0 μl injection into either the substantia innominate/nucleus basalis of Meynert (SI/NBM) or the medial septum/ventral diagonal band (MS/VDB).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Bernabe CS, Caliman IF, de Abreu ARR, Molosh AI, Truitt WA, Shekhar A, Johnson PL (2024) Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses. Transl Psychiatry 14(1):60. doi: 10.1038/s41398-024-02769-3 PMID: 38272876

Objective: To investigate the role of serotonergic inputs from the raphe nuclei to the perifornical hypothalamic area (PFA) in regulating panic and fear responses.

Summary: This study identifies a novel serotonergic system projecting to the PFA that inhibits innate panic and conditioned fear responses. The findings suggest that serotonergic inputs from the lateral wings of the dorsal and median raphe nuclei to the PFA represent a panic/fear-off circuit, which could also play a role in modulating reward behaviors.

Usage: Each rat (Adult Sprague-Dawley; 300–350 g) received two bilateral microinjections per site (100 nl each, 1 μM in ACSF) of either Anti-SERT-SAP (IT23) or the control Mouse IgG-SAP (IT-18) via an injector that was connected to bilateral guide-cannulas implanted into the PFA.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)