targeted-toxins

Boucher A (2024) Unveiling cholera toxin binding and intoxication using enteroids and site-specific mutants. Univ Gothenburg Thesis.

Objective: To investigate the binding site requirements of cholera toxin in the human body.

Summary: The cause of cholera symptoms is cholera toxin secreted by bacteria once in the small intestine. Cholera toxin has multiple binding sites that lead to many different intake mechanisms. By identifying the binding sites responsible, the study seeks to lay the groundwork for better means of treatment.

Usage: Leukocytes were treated with biotinylated Cholera toxin B binding-deficient mutants mixed with Streptavidin-SAP (IT-27) and assessed for cell death.

Related Products: CTB-SAP (Cat. #IT-14), Streptavidin-ZAP (Cat. #IT-27), Recombinant Cholera Toxin B (Cat. #PR-14)

Pandala N, Han I, Meyering E, Stone EM, Mullins RF, Tucker BA (2024) iPSC derived choroidal endothelial cell delivery using laminin-based hydrogels for the treatment of AMD. ARVO Annual Meeting 65(7):1542.

Objective: To demonstrate an interventional therapy for age-related macular degeneration (AMD) using a rat model.

Summary: In this study, induced pluripotent stem cells (iPSCs) were injected into the eyes of rats that had undergone Anti-CD105-SAP-induced choroidal cell death, mimicking the pathology of AMD. The efficacy of the iPSC treatment was evaluated by comparing donor cell survival, retention, and integration in treated eyes versus controls that did not receive iPSCs.

Usage: Anti-CD105-SAP (IT-80) was administered via supra-choroidal injection at a concentration of 0.05 mg/ml to selectively induce choroidal endothelial cell death.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

Han I, Pandala N, Haefeli L, Lang MJ, Stone EM, Mullins RF, Tucker BA (2024) Development of chemically induced choroidal injury models for the study and treatment of AMD. ARVO Annual Meeting 65(7):5382.

Objective: To describe the development of Age-Related Macular Degeneration (AMD) models through the targeted injury of choroidal cells in the eye.

Summary: Anti-CD38-SAP (BETA-016) and Anti-CD105-SAP (IT-80) were utilized to selectively lesion choroidal cells in the eyes of mice, creating an AMD model. Both agents demonstrated localized effects with no observed systemic toxicity at the administered doses, contrasting with the broader toxicity seen with Sodium Iodate, another lesioning agent examined.

Usage: Different doses of Anti-CD38-SAP and Anti-CD105-SAP (0.05, 0.25, and 0.5 mg/ml; 10 μL/eye) were injected suprachoroidally into the eyes of mice to induce the desired choroidal cell lesions.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Quiros-Ortega ME, Carretero-Rey M, Garcia-Garrido MF, López Téllez JF, Jiménez-Recuerda I, Muñoz de Leon López CA, Khan ZU (2024) Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit. CNS Neurosci Ther 30(4):e14727. doi: 10.1111/cns.14727 PMID: 38644593

Objective: Use OX7-SAP to create an object-recognition memory deficit model in rats.

Summary: Ventral pathway circuits are responsible for part of object recognition memory. Lesioning with OX7-SAP, a way to selectively remove CD90-expressing neuronal cells, can create a knockout model of object recognition memory, and lesioning in specific parts of the brain can construct a map of object recognition memory function.

Usage: Rats were lesioned with OX7-SAP in either the brain’s perirhinal cortex, frontal cortex, or Area V2 and assessed for object recognition memory deficits. (0.2μg in 1μL, IT-02)

Related Products: OX7-SAP (Cat. #IT-02)

Souza GMPR, Abbott SBG (2024) Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?. Respir Physiol Neurobiol 322:104217. doi: 10.1016/j.resp.2024.104217 PMID: 38237884

Objective: To discuss the current definition of chemoreceptor neurons in the retrotrapezoid nucleus (RTN) and describe how this definition has evolved over time.

Summary: Studies offer evidence that RTN neurons are indispensable for the central respiratory chemoreflex in mammals and exert a tonic drive to breathe at rest. Moreover, RTN has an interdependent relationship with oxygen sensing mechanisms for the maintenance of the neural drive to breathe and blood gas homeostasis. Collectively, RTN neurons are a genetically-defined group of putative central respiratory chemoreceptors that generate CO2-dependent drive that supports eupneic breathing and stimulates the hypercapnic ventilatory reflex.

Usage: One widely adopted approach to eliminate RTN neurons utilizes local microinjections of the ribosomal-toxin Saporin conjugated to the analogue of substance-P (SSP-SAP),which results in cell death of neurokinin receptor 1-expressing neurons in a concentration-dependent manner.

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Nattie EE et al. Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603-616, 2002.
• Souza GMPR et al. Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats. J Physiol 596(13):2521-2545, 2018.
• Takakura AC et al. Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585, 2014.
• Takakura AC et al. Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apneic threshold in rats. J Physiol 586:2975-2991, 2008.

Aerts EG (2024) Estradiol’s role in timely puberty onset in the ewe. Western Virginia Univ

Objective: To investigate the role of arcuate nucleus KNDy (kisspeptin/neurokinin B/dynorphin) neurons in regulating the timing of puberty onset and estradiol (E2) sensitivity in female sheep.

Summary: Ablation of approximately 75% of KNDy neurons using NKB-SAP in the arcuate nucleus significantly delayed puberty onset and blunted the luteinizing hormone (LH) surge, demonstrating that KNDy neurons are critical for timely puberty in ewes. However, animals retained the ability to respond to NK3R agonist senktide, suggesting upstream populations may mediate estradiol negative feedback.

Usage: NKB-SAP (IT-63) was bilaterally injected into the arcuate nucleus (1 µg/side in 1 µL) to ablate NK3R-expressing KNDy neurons and evaluate their role in pubertal timing and LH regulation.

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

Morroni F, Caccamo A (2024) Advances and Challenges in Gene Therapy for Alzheimer’s Disease. J Alzheimers Dis 101(s1):S417-S431. doi: 10.3233/JAD-230783 PMID: 39422937

Objective: Provide an overview of clinical and preclinical studies where gene therapy techniques have been utilized in the context of Alzheimer’s Disease (AD), highlighting their potential as novel therapeutic strategies.

Summary: Gene therapy offers the potential for long-term benefits by providing sustained therapeutic effects. By modifying or replacing faulty genes, it may slow down or halt the progression of AD. Vector-based genetic therapies have demonstrated promising results in mouse models, but face hurdles such as managing risks associated with vectors and delivery methods.

Usage: Rats with cholinergic deficit were induced by intraseptal injection of 192-IgG-SAP (IT-01).

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

See Also:

• Dobryakova YV et al. Intrahippocampal adeno-associated virus-mediated overexpression of nerve growth factor reverses 192IgG-saporin-induced impairments of hippocampal plasticity and behavior. Front Neurosci 15:745050, 2021.

Thomson AC (2024) Puberty-Associated Changes in Kiss1r, MC3R, and MC4R in the Ewe. West Virgina University

Objective: To examine kisspeptin receptor (Kiss1r) mRNA expression in gonadotropin releasing hormone (GnRH) neurons and melanocortin 3 and 4 receptor (MC3R/MC4R) expression in kisspeptin neurons across pubertal development.

Summary: Kiss1r expression in GnRH neurons increased with development. In the arcuate nucleus (ARC), the proportion of kisspeptin neurons expressing MC3R, but not MC4R, also rose, though MC3R signal intensity remained unchanged. ARC Kiss1r expression did not vary. Findings support increased GnRH neuron sensitivity to kisspeptin and aMSH as part of the pubertal neurocircuitry.

Usage: Author references prior studies. Deletion of about 75% of KNDy neurons through targeted NKB-SAP (IT-63) injections significantly delayed puberty onset. Reduction of Kiss1r expression in the ARC via targeted injection of a Kisspeptin-SAP (IT-102) conjugate disrupted pulsatile LH release and blocked the LH surge.

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

See Also:

• Aerts EG et al. 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, 2024.

Kudsi SQ, Viero FT, Pereira LG, Trevisan G (2024) Involvement of the transient receptor channels in preclinical models of musculoskeletal pain. Curr Neuropharmacol 22(1):72-87. doi: 10.2174/1570159X21666230908094159 PMID: 37694792

Objective: To provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models.

Summary: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.

Usage: NK1-expressing neurons were ablated by SP-SAP (neurotoxin saporin conjugated to substance P) to Vc, and the ablation of NK1-expressing second-order neurons reduced the MGS and bite force nociceptive behaviors.

Related Products: SP-SAP (Cat. #IT-07)

See Also:

• Wang S, Lim J, Joseph J, Wang S, Wei F, Ro JY, Chung MK. Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1. J Pain. 2017 Nov;18(11):1333-1345. doi: 10.1016/j.jpain.2017.06.005. Epub 2017 Jun 29. PMID: 28669862

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)