targeted-toxins

Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215

Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).

Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.

Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.

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

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

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

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421

Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).

Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.

Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.

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

Zhang H, Zhu Y, Chen S, Deng K, Zheng M, Zeng Z, Wang Q, Cai H, Lu Z (2023) Autonomic nerve and its modulation approaches for heart failure. Brain & Heart doi: 10.36922/bh.0913

Objective: Authors review neural modulation approaches that can assist in the management of heart failure.

Summary: The autonomic nervous system governs the heart’s neurological regulation through opposing functions of its sympathetic and parasympathetic components. Potential treatments for heart failure include inhibiting the sympathetic nerve’s overactivity and restoring parasympathetic activity in the heart. CTB-SAP was used to ablate cardiac sympathetic neurons via retrograde transport on stellate ganglion neurons.

Usage: CTB-SAP was injected into the right superior vervical ganglion of adult male Sprague-Dawley rats (50 ug/rat).

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

See Also:

• Llewellyn-Smith IJ et al. Retrogradely transported CTB-saporin kills sympathetic preganglionic neurons. Neuroreport 10(2):307-312, 1999.

Canarutto D, Omer Javed A, Pedrazzani G, Ferrari S, Naldini L (2023) Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation. Br Med Bull ldad017. doi: 10.1093/bmb/ldad017 PMID: 37460391

Objective: The authors review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.

Summary: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient’s. Ex vivo HSC gene therapy (HSC GT) is a form of HSCT in which HSCs are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow niche, which is required for the engraftment of infused cells. One approach reviewed by the authors involves Anti-CD45-SAP. The conjugate was shown to clear the white blood cell compartment. Administration into mice prior to HSCT resulted in comparable haematopoietic reconstitution as total body irradiation, with less side effects (Palchaudhuri R. et al, 2016) and faster T-cell repopulation likely due to sparing radio damage to the thymic stroma (Schiroli G et al., 2017).

Related Products: Anti-CD45.2-SAP (Cat. #IT-91)

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Schiroli G et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9(411):eaan0820, 2017.

Low ZXB, Lee XR, Soga T, Goh BH, Alex D, Kumari Y (2023) Cannabinoids: Emerging sleep modulator. Biomed Pharmacother 165:115102. doi: 10.1016/j.biopha.2023.115102 PMID: 37406510

Objective: To review the modulation of sleep by cannabinoids and the endocannabinoid system.

Summary: This review article discusses the role of cannabinoids, including endocannabinoids like anandamide and phytocannabinoids like THC and CBD, in regulating the sleep-wake cycle. The authors review evidence that cannabinoids act on areas of the brain involved in promoting sleep, like the ventrolateral preoptic nucleus, and inhibit wake-promoting areas, like the locus coeruleus.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023

Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.

Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.

Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

Souza GMPR, Stornetta DS, Shi Y, Lim E, Berry FE, Bayliss DA, Abbott SBG (2023) Neuromedin B-expressing neurons in the retrotrapezoid nucleus regulate respiratory homeostasis and promote stable breathing in adult mice. J Neurosci JN-RM-0386-23. doi: 10.1523/JNEUROSCI.0386-23.2023 PMID: 37290937

Objective: To develop a transgenic mouse model and demonstrate that retrotrapezoid nucleus (RTN) neurons are fundamental for respiratory homeostasis and mediate the stimulatory effects of CO2 on breathing.

Summary: This study uses a transgenic Nmb-Cre mouse model to demonstrate that RTNNmb neurons are crucial for CO2-dependent breathing in mice. It provides evidence that these neurons play a key role in respiratory homeostasis and might be linked to sleep-disordered breathing in humans. Cre-dependent cell ablation and optogenetics show RTNNmb neurons’ essential function in mediating the hypercapnic ventilatory response, highlighting the importance of these neurons in maintaining eupneic breathing.

Usage: This publication references the use of SSP-SAP (IT-11) to target RTN neurons.

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

See Also:

• 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.

Harris RBS (2023) Low dose peripheral leptin infusion produces selective activation of ventromedial hypothalamic and hindbrain STAT3. Am J Physiol Endocrinol Metab doi: 10.1152/ajpendo.00083.2023 PMID: 37285599

Objective: To show that the deletion of leptin-receptor expressing cells in the ventromedial hypothalamus (VMH) has no effect on basal body weight or body fat mass, but greatly attenuates the inhibition of food intake.

Summary: This study evaluates leptin’s impact on hypothalamic pSTAT3 in leptin-infused versus injected rats. High-dose leptin suppressed food intake and reduced weight and fat mass without affecting energy metrics, with pSTAT3 increases observed in the VMH only during intake suppression and in the nucleus of the solitary tract over both short and extended periods. These results highlight the role of VMH and hindbrain receptors in mediating leptin’s effects on food intake and metabolic changes.

Usage: Leptin-SAP is referenced in Seamon et al 2019: Male Sprague-Dawley rats received bilateral VMH 75 nl injections of 260 ng/microliter of Leptin-SAP (IT-47) or Blank-Saporin (IT-21).

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

See Also:

• Seamon M et al. Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. Am J Physiol Endocrinol Metab 317(4):E586-E596, 2019.

Keilholz A, Homan C, Schroeder A, Osman K, Smith C, Pathak I, Streeter K, Ozden I, Ma L, Lever T, Nichols N (2023) Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss. American Physiology Summit 2023 Meeting Abstracts 38(S1)

Objective: Examine if upper airway function/coordination can be improved in lower motor neuron (LMN) degeneration by tongue exercise-induced axis plasticity.

Summary: Tongue muscle weakness in patients with motor neuron diseases suggests a potential role for therapeutic exercise but lacks evidence due to lack of an appropriate model. Data suggests that tongue exercise in CTB-SAP rats results in enhanced XII motor plasticity and mitigates structural airway changes. In conclusion, tongue exercise appears to cause XII-tongue axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration.

Usage: The authors developed a novel rodent model using intralingual injections of CTB-SAP to induce targeted loss of XII motor neurons and motor output.

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