targeted-toxins

Ketabforoush A, Wang M, Smith C, Arnold WD, Nichols N (2024) Longitudinal assessment of outcome measures of diaphragm motor unit connectivity as biomarkers of phrenic motor unit degeneration and compensation. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.1402

Objective: Using CTB-SAP to lesion motor neurons and measuring motor neuron connectivity and cell death, as a model for phrenic motor neuron degeneration.

Summary: Processes such as injury or aging can affect motor neurons and cause degeneration. CTB-SAP is used to mimic this phenomenon and is used to cause motor degeneration in the diaphram of rats. The motor neurons and motor units have plasticity and the ability to compensate for this damage and the authors seek to use the created rat model to measure this motor unit connectivity.

Usage: Rats received bilateral intrapleural injections of 25 μg of CTB-SAP (IT-14) as well as 25 more μg of free CTB. Control mice received 25 μg of free saporin and 25 μg of CTB.

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

Janes T, Cardani S, Pagliardini S (2024) The progestinic drug, etonogestrel, rescues breathing in a rodent model of central chemoreflex impairment. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.978

Objective: Assessing the efficacy of etonogestrel as a treatment to congenital hypoventilation syndrome (CCHS).

Summary: Etonogestrel can stimulate breathing and CO2-chemoreflexes and could be used to treat congenital hypoventilation syndrome. A model of CCHS was created in rats through the ablation of retrotrapezoid nucleus neurons with substance-P saporin. In this CCHS model-rat Etonogestrel was assessed for its ability to return breathing back to normal and for its mechanism of action.

Usage: Rats were lesioned with SSP-SAP [IT-11] targeting the retrotrapezoid nucelus (R.V.N.) neurons.

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

Kniffin A, Bangasser DA, Parikh V (2024) Septohippocampal cholinergic system at the intersection of stress and cognition: Current trends and translational implications. Eur J Neurosci 59(9):2155-2180. doi: 10.1111/ejn.15999 PMID: 37118907

Objective: Review current research highlighting the contributions of cholinergic septohippocampal pathway (SHP) in modulating memory encoding, consolidation, and retrieval.

Summary: Authors presented evidence generated from empirical research and computational modeling approaches that suggest cholinergic SHP modulate distinct components of episodic memory. Specifically, higher levels of septohippocampal ACh and downstream activation of specific subtypes of mAChRs/nAChRs in local circuits of hippocampal networks reduce interference and enhance encoding, while lower cholinergic signaling facilitate memory consolidation by gating information to the neocortex.

Usage: Rats with cholinergic deficit in the SHP pathway were induced by injection with 192-IgG-SAP (IT-01).

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

See Also:

• Baxter MG et al. Intact spatial learning following lesions of basal forebrain cholinergic neurons. NeuroReport 7:1417-1420, 1996.
• Baxter MG et al. Intact spatial learning in both young and aged rats following selective removal of hippocampal cholinergic input. Behav Neurosci 110:460-467, 1996.
• Bizon JL et al. Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze. Hippocampus 13(6):676-684, 2003.
• Frick KM et al. Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning. Hippocampus 14:244-254, 2004.

Ogata J, Shimada Y, Ohashi T, Kobayashi H (2024) Usefulness of antibody-drug conjugate as preconditioning for hematopoietic stem cell-targeted gene therapy in wild-type and Fabry disease mouse models. Mol Genet Metab 142(3):108494. doi: 10.1016/j.ymgme.2024.108494 PMID: 38820907

Objective: To develop a saporin/antibody-based conditioning for hematopoietic stem cell-targeted gene therapy for use in models of Fabry Disease.

Summary: Fabry disease is characterized by deficient activity of α-galactosidase A (GLA). Consequently, globotriaosylceramide (Gb3) accumulates in various organs causing damage. Fabry Disease is treatable with hematopoietic stem cell therapy which requires strong conditioning, but that can often be associated with side effects. CD45-SAP is investigated as a conditioning agent for these stem cells.

Usage: CD45-SAP was used in hematopoietic stem cells in a mice model of Fabry Disease.

Meng XT, Song SY, Li Y, Peng S, Zhang LC (2024) Activation of alpha 2 adrenergic receptor of cerebrospinal fluid-contacting nucleus alleviates acute incision pain behavior in rats. Research Square doi: 10.21203/rs.3.rs-4258857/v1

Objective: To study the effects of Dexmedetomidine (DEX) on pain modulation.

Summary: Dexmedetomidine is an alpha 2-adrenergic receptor agonist with sedative, analgesic, and anti-anxiety effects. DEX was analyzed for its effects using a pain neuron knockout model of rats created by ablation of cerebrospinal fluid contacting neurons in the lateral ventricles of rats. DEX inhibited the pain behavior of rats in a dose-dependent manner, and the analgesic effect of DEX was significantly attenuated in CSF-contacting nucleus “knockout” rats.

Usage: CTB-SAP [IT-14] (0.5 µg in 3 µL) was injected into the lateral ventricles (L.V.) of rats over 10 minutes.

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

Shivakumar AB, Mehak SF, Jijimon F, Gangadharan G (2024) Extra-hippocampal contributions to social memory: The role of septal nuclei. Biol Psychiatry 6:835-847. doi: 10.1016/j.biopsych.2024.04.018 PMID: 38718881

Objective: Review neural circuit mechanisms that underlie social memory, with a special emphasis on the septum.

Summary: Understanding the complexities of the septohippocampal axis will allow targeted therapies to be developed to improve social memory deficits and enhance overall cognitive function.

Usage: Medial septum lesions in rats with 192-IgG-SAP (IT-01).

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

See Also:

• Vale-Martinez A et al. Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats. Eur J Neurosci 16(6):983-998, 2002.
• Berger-Sweeney J, Stearns NA, Frick KM, Beard B, Baxter MG (2000) Cholinergic basal forebrain is critical for social transmission of food preferences. Hippocampus 10(6):729-738. doi: 10.1002/1098-1063(2000)10:6<729::AID-HIPO1010>3.0.CO;2-M PMID: 11153718

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)