targeted-toxins

Guo SS, Gong Y, Zhang TT, Su XY, Wu YJ, Yan YX, Cao Y, Song XL, Xie JC, Wu D, Jiang Q, Li Y, Zhao X, Zhu MX, Xu TL, Liu MG (2024) A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch. Sci Adv 10(33):eadn6272. doi: 10.1126/sciadv.adn6272 PMID: 39150998

Objective: To investigate anxiety-like behaviors in mouse models of chronic itch and identify lateral septum (LS) GABAergic neurons as key mediators through thalamic and hypothalamic circuit interactions.

Summary: Chronic itch amplifies excitatory inputs from the thalamic nucleus reuniens to LS GABAergic neurons, promoting anxiety-like behaviors. Inhibiting the Re → LS circuit reduces anxiety related to chronic itch but not restraint stress, highlighting its specificity. LS GABAergic neurons suppress lateral hypothalamus activity to mediate chronic itch-induced anxiety, with Bombesin-SAP targeting spinal itch neurons to confirm this pathway’s role.

Usage: Mice were intrathecally injected with Bombesin-SAP (IT-40) (400 ng/5 μl). Blank-SAP (IT-21) (400 ng/5 μl) was administered similarly to a control.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

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.abq5585

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)

Kwok CHT, Harding EK, Burma NE, Markovic T, Massaly N, van den Hoogen NJ, Stokes-Heck S, Gambeta E, Komarek K, Yoon HJ, Navis KE, McAllister BB, Canet-Pons J, Fan C, Dalgarno R, Gorobets E, Papatzimas JW, Zhang Z, Kohro Y, Anderson CL, Thompson RJ, Derksen DJ, Morón JA, Zamponi GW, Trang T (2024) Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry. Nat Commun 15(1):6264. doi: 10.1038/s41467-024-50657-7 PMID: 39048565

Objective: To show that pannexin-1 (Panx1) channels expressed on microglia critically modulate LC activity during opioid withdrawal.

Summary: The findings demonstrate that microglial Panx1 channels modulate LC noradrenergic circuitry during opioid withdrawal and reinstatement. Blocking Panx1 to dampen LC hyperexcitability may, therefore, provide a therapeutic strategy for alleviating the physical and aversive components of opioid withdrawal.

Usage: Mac-1-SAP (IT-06) was injected through the cannula (15 µg) for three consecutive days before systemic naloxone administration.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Bryder D, Konturk-Ciesla A, Zhang Q, Kharazi S (2024) A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Research Square doi: 10.21203/rs.3.rs-4528815/v1

Objective: To develop a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated Hematopoietic stem cell.

Summary: Authors demonstrate that young HSCs, once transplanted, survive and thrive in aged hosts, dramatically improving hematopoietic output and ameliorating age-compromised lymphopoiesis.

Usage: Intravenous injection of CD45-SAP (3 mg/kg, IT-91). Biotinylated anti-CD45.2 antibodies were mixed with streptavidin-saporin conjugate at a 1:1 molar ratio (IT-27).

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)

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)

Garaudé S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, Dell’ Aglio A, Juskevicius D, Zuin J, Burgold T, Wang S, Katta V, Manquen G, Li Y, Larrue C, Camus A, Durzynska I, Wellinger LC, Kirby I, Van Berkel PH, Kunz C, Tamburini J, Bertoni F, Widmer CC, Tsai SQ, Simonetta F, Urlinger S, Jeker LT (2024) Selective haematological cancer eradication with preserved haematopoiesis. Nature 630(8017):728-735. doi: 10.1038/s41586-024-07456-3 PMID: 38778101

Objective: To demonstrate that an antibody–drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specifc depletion of the entire haematopoietic system, including Haematopoietic stem cells ( HSC).

Summary: Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type.

Usage: For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody (BC8 or MIRG451 mAbs) and saporin–streptavidin (IT-27) at a 1:1 molar ratio for 30 min at room temperature

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)

Loften A (2024) Cholinergic modulation of dopamine-related effects of ethanol in the rat. Univ Gothenburg Thesis.

Objective: To explore the role of acetylcholine and cholinergic interneurons (CIN) in ethanol-induced dopamine (DA) release and in the reinforcing effects of ethanol.

Summary: The author’s thesis supports an important role of accumbal CIN in ethanol ́s DA releasing and reinforcing effects, opening up for new potential pharmacological targetsfor treatments of alcohol use disorder.

Usage: in vivo rat model with depletion of accumbal CIN was developed utilizing anti-choline acetyltransferase-saporin (IT-42)

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

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)

Toledo C, Del Rio R (2024) Cardiorespiratory disturbances in Alzheimer’s disease: A focus on the contribution of sympathetic premotor neurons. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.2540

Objective: To characterize cardiorespiratory function in AD patients and then to determine the role of RVLM-C1 neurons in autonomic and sleep-disordered breathing in APP/PS1 double transgenic mice, and experimental model showing AD-like pathology.

Summary: Results show that RVLM-C1 neurons play a main role in the development/maintenance of cardiorespiratory disorders in experimental AD.

Usage: Bilateral stereotaxic injections of Anti-DBH-SAP (IT-03) into the RVLM were used to selectively destroy C1 neurons.

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

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