targeted-toxins

Li Y, Bao Y, Zheng H, Qin Y, Hua B (2021) Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction. Biomed Pharmacother 139:111653. doi: 10.1016/j.biopha.2021.111653

Summary: In this review the authors discuss the important role Src protein tyrosine kinase plays in the adverse consequences of clinical application of opioids

Usage: Intrathecal injection of Mac-1-SAP depletes microglial cells in the spinal dorsal horn and alleviates the loss of anti-nociception of morphine and prevents the decrease in morphine potency. This demonstrates that spinal microglial cells are necessary for morphine tolerance (15 µg; Leduc-Pessah et al., 2017).

See: Leduc-Pessah H et al. Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance. J Neurosci 37:10154-10172, 2017.

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

Gross C (2021) PARVing the way to cap translation for seizure control. Epilepsy Curr 21(5):360-362. doi: 10.1177/15357597211027010

Summary: Loss of GABAergic interneurons leads to spontaneous recurrent seizures that persist over months if the amount and spatial spread of initial inhibitory neuron loss is sufficient.

Usage: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.

See: Chun E et al. Targeted hippocampal GABA neuron ablation by Stable Substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57, 2019.

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

Middleton SJ, Barry AM, Comini M, Li Y, Ray PR, Shiers S, Themistocleous AC, Uhelski ML, Yang X, Dougherty PM, Price TJ, Bennett DL (2021) Studying human nociceptors: from fundamentals to clinic. Brain 144(5):1312-1335. doi: 10.1093/brain/awab048

Summary: The authors injected 5 µg of IB4-SAP into the sciatic nerve in the left thigh. Lesioned animals displayed attenuated NGF-induced hyperalgesia, as well as differences in other pain-model markers.

See: Tarpley JW et al. The behavioral and neuroanatomical effects of IB(4)-saporin treatment in rat models of nociceptive and neuropathic pain. Brain Res 1029(1):65-76, 2004.

Related Products: IB4-SAP (Cat. #IT-10)

Petrosini L, De Bartolo P, Cutuli D (2021) Neurotoxic effects, mechanisms, and outcome of 192 IgG-Saporin lesions. RM Kostrzewa (Ed.): Handbook of Neurotoxicity . Springer, Cham doi: 10.1007/978-3-030-71519-9_79-1

Summary: 192-IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Immunotoxic lesions by 192-IgG-saporin represent a valid animal model of Alzheimer’s disease, given the degeneration of basal cholinergic system present in this pathology. The selective lesioning of cholinergic innervation by means of 192-IgG-saporin (injected i.p. or i.c.v.) is able to interfere with experience-dependent plasticity.

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

Llorente-Ovejero A, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, González de San Román E, Manuel I, Giralt MT, Rodríguez-Puertas R (2021) Specific phospholipid modulation by muscarinic signaling in a rat lesion model of Alzheimer’s disease. ACS Chem Neurosci 12(12):2167-2181. doi: 10.1021/acschemneuro.1c00169 PMID: 34037379

Objective: To evaluate the lipid composition and muscarinic signaling in brain areas related to cognitive processes.

Summary: Using a rat model of BFCN lesion, this study evaluated the lipid composition and muscarinic signaling in brain areas related to cognitive processes. Results suggest that the modulation of specific lipid metabolic routes could represent an alternative therapeutic strategy to potentiate cholinergic neurotransmission and preserve cell membrane integrity in AD.

Usage: 192-IgG-SAP was dissolved in aCSF under aseptic conditions to a final concentration of 130 ng/ml. aCSF or 192-IgG-SAP was bilaterally injected (1 ml/hemisphere) at a constant rate of 0.2 ml/min. to selectively eliminate BFCN in the NBM.

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

See Also:

• Llorente-ovejero A et al. Increase in cortical endocannabinoid signaling in a rat model of basal forebrain cholinergic dysfunction. Neuroscience 362:206-218, 2017.

Vicario N, Spitale FM, Tibullo D, Giallongo C, Amorini AM, Scandura G, Spoto G, Saab MW, D’Aprile S, Alberghina C, Mangione R, Bernstock JD, Botta C, Gulisano M, Buratti E, Leanza G, Zorec R, Vecchio M, Di Rosa M, Li Volti G, Lazzarino G, Parenti R, Gulino R (2021) Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing. Cell Death Dis 12(7):625. doi: 10.1038/s41419-021-03907-1

Summary: The focal removal of confined populations of spinal MNs by injection of CTB-SAP has proven to be useful in mimicking respiratory dysfunction, dysphagia, and focal MN loss.

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

See Also:

• Lind LA et al. Tongue and hypoglossal morphology after intralingual cholera toxin B-saporin injection. Muscle Nerve 63(3):413-420, 2021.
• Gulino R et al. Neuromuscular plasticity in a mouse neurotoxic model of spinal motoneuronal loss. Int J Mol Sci 20(6):1500, 2019.
• Nichols N et al. Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29, 2015.
• Gulino R et al. Expression of cell fate determinants and plastic changes after neurotoxic lesion of adult mice spinal cord by cholera toxin-B saporin. Eur J Neurosci 31(8):1423-1434, 2010.

Vikan AK, Kostas M, Haugsten EM, Selbo PK, Wesche J (2021) Efficacy and selectivity of FGF2-saporin cytosolically delivered by PCI in cells overexpressing FGFR1. Cells 10(6):1476. doi: 10.3390/cells10061476

Summary: Fibroblast growth factor receptors (FGFRs) have become an attractive target in cancer research and therapy due to their implication in several cancers. The authors evaluated the efficacy and selectivity of PCI of FGF2-saporin (FGF-SAP) in cells overexpressing FGFR1. The authors conclude that to prevent off-target effects of FGF-based toxins, it will be necessary to circumvent binding to HSPGs, for example by mutating the binding site of FGF2 to HSPGs.

Related Products: FGF-SAP (Cat. #IT-38)

Maejima Y, Yokota S, Shimizu M, Horita S, Kobayashi D, Hazama A, Shimomura K (2021) The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity. Nutr Metab (Lond) 18(1):58. doi: 10.1186/s12986-021-00582-z

Summary: Feeding rhythm disruption contributes to the development of obesity. GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination.

Usage: Exenatide-SAP targets GLP-1R expressing cells. Injections of 0.1 μg/0.5 μl Ex4-SAP or 0.1 μg/0.5 μl Blank-SAP (control) were administered into the DMH.

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-SAP (Cat. #IT-21)

Fujii T, Lee EJ, Miyachi Y, Yamasaki R, Lim YM, Iinuma K, Sakoda A, Kim KK, Kira JI (2021) Antiplexin D1 antibodies relate to small fiber neuropathy and induce neuropathic pain in animals. Neurol Neuroimmunol Neuroinflamm 8(5):e1028. doi: 10.1212/NXI.0000000000001028

Summary: NeP patient-derived plexin D1-IgG selectively binds to isolectin B4-positive unmyelinated C-fiber type small DRG neurons that sense mechanical pain.

See: Tarpley JW et al. The behavioral and neuroanatomical effects of IB(4)-saporin treatment in rat models of nociceptive and neuropathic pain. Brain Res 1029(1):65-76, 2004.

Related Products: IB4-SAP (Cat. #IT-10)

Taxini CL, Marques DA, Bícego KC, Gargaglioni LH (2021) A5 noradrenergic neurons and breathing control in neonate rats. Pflugers Arch 473(6):859-872. doi: 10.1007/s00424-021-02550-1

Summary: In this study, the authors investigated the participation of A5 noradrenergic neurons in neonates (P7-8 and P14-15) in the control of ventilation during hypoxia and hypercapnia. data suggest that noradrenergic neurons of the A5 region in neonate rats do not participate in the control of ventilation under baseline and hypercapnic conditions, but exert an inhibitory modulation on breathing variability under hypoxic challenge in early life (P7-8).

Usage: Anti-DBH-SAP (420 ng/μL) or saporin (SAP, control) was injected into the A5 region of neonatal male Wistar rats.

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