targeted-toxins

Li F, Jiang H, Shen X, Yang W, Guo C, Wang Z, Xiao M, Cui L, Luo W, Kim BS, Chen Z, Huang AJW, Liu Q (2021) Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell 184(14):3762-3773.e10. doi: 10.1016/j.cell.2021.05.017

Objective: To test the hypothesis that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing.

Summary: Chemical activation of neuromedin B (NMB)-sensitive neurons elicits action potentials in caudal ventral respiratory group (cVRG) neurons and leads to sneezing behavior. This study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.

Usage: Microinjection of NMB-saporin into the sneeze-evoking region abolished the sneezing responses to capsaicin and histamine.

Related Products: NMB-SAP (Cat. #IT-70)

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)

Kucinski A, Sarter M (2021) Reduction of falls in a rat model of PD falls by the M1 PAM TAK-071. Psychopharmacology (Berl) 238(7):1953-1964. doi: 10.1007/s00213-021-05822-x

Summary: In addition to the disease-defining motor symptoms, patients with Parkinson’s disease (PD) exhibit gait dysfunction, postural instability, and a propensity for falls. The muscarinic M1-positive allosteric modulator (PAM) TAK-071 improves the attentional performance of rats with BF cholinergic losses. The authors previously developed a rodent model of PD falls by demonstrating that rats with dual basal forebrain cholinergic and mediodorsal striatal dopamine losses (“DL rats”) exhibit a heightened fall rate when required to traverse dynamic surfaces. This study tested the hypothesis that TAK-071 reduces fall rates in DL rats.

Usage: Rats received bilateral infusions of 192-IgG-SAP (200 ng/μL; 0.8 μL/hemisphere) or an equal volume of artificial cerebral spinal fluid into the nucleus basalis and substantia innominata of the basal forebrain.

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

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)

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)