History of Saporin

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)

Bolshakov AP, Stepanichev MY, Dobryakova YV, Spivak, YS, Markevich, VA (2020) Saporin from Saponaria officinalis as a tool for experimental research, modeling, and therapy in neuroscience. Toxins (Basel) 12(9):546. doi: 10.3390/toxins12090546

Summary: A review of studies where saporin-based conjugates were used to analyze cell mechanisms of sleep, general anesthesia, epilepsy, pain, and development of Parkinson’s and Alzheimer’s diseases.

Related Products: Targeted Toxins

Landrigan J, Dwyer Z, Beauchamp S, Rodriguez R, Fortin T, Hayley S (2020) Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration. NeuroToxicology 76:153-161. doi: 10.1016/j.neuro.2019.11.007 PMID: 31738977

Objective: To assess the impact of Quantum Dots (QDs) alone and QDs conjugated to Saporin, on substantia nigra microglia and dopamine neurons.

Summary: QDs might be a viable route for toxicant delivery and also have an added advantage of being fluorescently visible. Ultimately, we found SNc neurons to be exceptionally vulnerable to QD-saporin and suggest that this could be a novel targeted approach to model Parkinson’s Disease-like inflammatory pathology.

Usage: Biotin-labeled saporin chicken polyclonal was mixed with QDs coated with streptavidin. 2  μl of QDs (1 μM) were mixed with 2  μL of biotinylated saporin (56 μM) and 76  μL of phosphate buffer solution was added.

Related Products: Saporin Chicken Polyclonal, affinity-purified biotin-labeled (Cat. #AB-17APBT)

Verkhratsky A, Parpura V, Rodriguez-Arellano J, Zorec R (2019) Astroglia in Alzheimer’s Disease. (eds. Verkhratsky A, Ho M, Zorec R, Parpura V). In: Advances in Experimental Medicine and Biology: Neuroglia in Neurodegenerative Diseases. 1175:273-324. Springer, Singapore. doi: 10.1007/978-981-13-9913-8_11

Summary: A review of the tools for creating animal models of Alzheimer’s Disease. 192-IgG-SAP binds selectively and irreversibly to low-affinity nerve growth factor receptor interrupting cholinergic neuronal protein synthesis was employed. Anti-DBH-SAP binds dopamine-β-hydroxylase, which is not only localized mainly in the cytosol, but also at the plasma membrane surface of noradrenergic neurons. Anti-DBH-SAP produced specific and dose-dependent depletions of locus coeruleus neurons, with no effects on other cholinergic, dopaminergic or serotonergic neuronal populations. The possibility to induce a partial or total noradrenergic loss (by varying the injected dose) makes this immunotoxic approach an ideal model to study events within the noradrenergic projection system, as they occur during age-related demise of locus coeruleus in humans.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Giansanti F, Flavell DJ, Angelucci F, Fabbrini MS, Ippoliti R (2018) Strategies to improve the clinical utility of saporin-based targeted toxins. Toxins (Basel) 10(2):82. doi: 10.3390/toxins10020082

Diepenbroek C, Quinn D, Stephens R, Zollinger B, Anderson S, Pan A, de Lartigue G (2017) Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352. doi: 10.1152/ajpgi.00095.2017

Objective: To develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons.

Summary: CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact.

Usage: In vitro: each well was treated with a different dose of saporin conjugates (0, 2.4, 24, or 240 ng) for 24 h. In vivo: An equal volume (rat: 1 µl; mouse: 0.5 µl) of CCK-SAP (250 ng/µl) or Saporin (250 ng/µl) was injected at two sites rostral and caudal to the laryngeal nerve branch.

Related Products: CCK-SAP (Cat. #IT-31)

Helena C, Toporikova N, Kalil B, Stathopoulos A, Pogrebna V, Carolino R, Anselmo-Franci J, Bertram R (2015) KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213. doi: 10.1210/en.2015-1070

Summary: Maturation and reproductive function in mammals is controlled by the kisspeptin neuropeptide. Kisspeptin modulates numerous systems within this framework including the mediation of positive and negative feedback effects of estradiol on luteinizing hormone (LH). In the rat, two kisspeptin neuronal populations exist; one in the anteroventral periventricular nucleus (AVPV), and the KNDy (kisspeptin/ neurokinin B/dynorphin) neurons in the arcuate nucleus. In this work the authors examine the role of KNDy neurons in estradiol positive feedback effects by administering 10-ng bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus of rats. The results indicate that KNDy neurons use dynorphin to inhibit AVPV neurons, establishing a regulatory mechanism for the amplitude of steroid-induced LH surges.

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

Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, Mulder J, Luiten PG, Xu ZD, Runesson J, Langel U, Lu B, Hokfelt T, Harkany T (2014) GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain. Cereb Cortex 24(12):3277-3288. doi: 10.1093/cercor/bht192

Summary: In this work the authors sought to clarify the role of galanin during brain development. Several different techniques were used including the use of Galanin-SAP (Cat. #IT-34) on primary cell cultures from the fetal forebrains of rats. Cultured basal forebrain neurons were exposed to 5 ng/ml of Galanin-SAP for 8 hours, and cell death was assessed after 72 hours. Cholinergic cells were killed by Galanin-SAP, indicating that these neurons can use extracellular galanin-2 receptors to facilitate development.

Related Products: Galanin-SAP (Cat. #IT-34)

Lappi DA, Stirpe F (2014) Ribosome-inactivating proteins in cancer treatment. (eds. F. Stirpe, D.A. Lappi). In: Ribosome-inactivating Proteins 244-252. doi: 10.1002/9781118847237.ch16

Ye Y, Bae S, Viet CT, Troob S, Bernabe D, Schmidt BL (2014) IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5. doi: 10.1186/1744-9081-10-5

Objective: To evaluate subtypes of sensory neurons involved in cancer pain and proliferation.

Summary: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Usage: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Haddad G, Zhu LF, Rayner DC, Murray AG ( 2013 ) Experimental glomerular endothelial injury in vivo. PLoS One 8(10):e78244 . doi: 10.1371/journal.pone.0078244

Related Products: MOA-SAP (Cat. #IT-92)

Mishra SK, Hoon MA (2013) The cells and circuitry for itch responses in mice. Science 340(6135):968-971. doi: 10.1126/science.1233765

Summary: Although previous work implicated neurons expressing the GRP (gastrin-releasing peptide) receptor were in the pruritic, or itch pathway, transgenic mice lacking natriuretic polypeptide b (Nppb) were almost completely insensitive to itch. Using the custom conjugate Nppb-SAP (Cat. #IT-69), the authors eliminated itch in response to a wide range of pruritic substances in normal mice through the administration of 5 μg of conjugate into the intrathecal space. Even after this lesion, the scratching response to intrathecal GRP was not changed, indicating that the role of GRP is at a later stage than previously hypothesized.

Related Products: Nppb-SAP (Cat. #IT-69)

Mishra SK, Holzman S, Hoon MA (2012) A nociceptive signaling role for neuromedin B. J Neurosci 32(25):8686-8695. doi: 10.1523/JNEUROSCI.1533-12.2012

Summary: Previous work suggests that neuromedin B (NMB) is involved in nociception. Direct injection of the peptide causes nociceptive sensitization, while NMB antagonists attenuate sensitization in reponse to nerve stimulation with mustard oil. Specific subsets of dorsal horn interneurons were eliminated by administering either 10 μg of the custom conjugate neuromedin B-SAP, 0.13 μg of SSP-SAP (Cat. #IT-11), or 1.3 μg of bombesin-SAP (Cat. #IT-40). Blank-SAP (Cat. #IT-21) was used as a control. The data indicate that NMB may be involved in the perception of thermal sensation, but not mechanical or pruritic sensation.

Related Products: NMB-SAP (Cat. #IT-70), SSP-SAP (Cat. #IT-11), Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Li AJ, Wiater MF, Oostrom MT, Smith BR, Wang Q, Dinh TT, Roberts BL, Jansen HT, Ritter S (2012) Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302(11):R1313-26. doi: 10.1152/ajpregu.00086.2012

Summary: It is clear that the arcuate nucleus (Arc) plays an important role in the generation of feeding rhythms. To clarify how this region modulates signals governing food intake the authors took advantage of the Arc mediation of leptin. Rats received bilateral injections of leptin-SAP (Cat. #IT-47, 56.5 ng per dose) into each Arc. Blank-SAP (Cat. #IT-21) was used as a control. The lesioned animals quickly became obese and displayed arrhythmic eating patterns under normal light conditions. The results indicate that lesioned neurons in the Arc as well as those in the suprachiasmatic nuclei are required for maintenance of feeding rhythms controlled by photic cues.

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

Antonucci F, Alpár A, Kacza J, Caleo M, Verderio C, Giani A, Martens H, Chaudhry FA, Allegra M, Grosche J, Michalski D, Erck C, Hoffmann A, Harkany T, Matteoli M, Härtig W (2012) Cracking down on inhibition: Selective removal of GABAergic interneurons from hippocampal networks. J Neurosci 32(6):1989-2001. doi: 10.1523/JNEUROSCI.2720-11.2012

Related Products: Anti-vGAT-SAP (Cat. #IT-71)

Polito L, Bortolotti M, Pedrazzi M, Bolognesi A (2011) Immunotoxins and other conjugates containing saporin-s6 for cancer therapy. Toxins (Basel) 3(6):697-720. doi: 10.3390/toxins3060697

Laplante F, Lappi DA, Sullivan RM (2011) Cholinergic depletion in the nucleus accumbens: Effects on amphetamine response and sensorimotor gating. Prog Neuropsychopharmacol Biol Psychiatry 35(2):501-509. doi: 10.1016/j.pnpbp.2010.12.005

Summary: Disruption of dopamine and acetylcholine balance in the striatum may play a role in conditions such as Parkinson’s and schizophrenia. In this work the authors lesioned cholinergic neurons in the nucleus accumbens (N.Acc) with the novel toxin Anti-ChAT-SAP (Cat. #IT-42). Rats received 0.25-µg bilateral injections of the toxin into the N.Acc. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The results of this lesion produced responses that may parallel the loss of cholinergic neurons seen in schizophrenia.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Baskin DG, Kim F, Gelling RW, Russell BJ, Schwartz MW, Morton GJ, Simhan HN, Moralejo DH, Blevins JE (2010) A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology 151(9):4207-4213. doi: 10.1210/en.2010-0295

Summary: There is evidence to suggest that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain can inhibit food intake by augmenting the cholecystokinin satiety response. In order to add support to this hypothesis the authors used oxytocin-SAP (Cat. #IT-46) to eliminate oxytocin receptive cells in the NTS. Blank-SAP (Cat. #IT-21) was used as a control. 0.5 µl-injections of oxytocin-SAP into the NTS caused reduced satiation effect of CCK-8 and blocked the stimulation of food intake by an oxytocin receptor antagonist.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Lyu MA, Rai D, Ahn KS, Sung B, Cheung LH, Marks JW, Aggarwal BB, Aguiar RC, Gandhi V, Rosenblum MG (2010) The rGel/BLyS fusion toxin inhibits diffuse large B-cell lymphoma growth in vitro and in vivo. Neoplasia 12(5):366-375. doi: 10.1593/neo.91960

Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF (2009) Cellular basis of itch sensation. Science 325:1531-1534. doi: 10.1126/science.1174868

Summary: Whether itch and pain use separate neuronal pathways has long been a subject of debate. The authors injected 400 ng of bombesin-SAP (Cat. #IT-40) into the intrathecal space of mice and examined itch and pain behavior. Lesioned mice had dramatic deficits in all itch behavior tested regardless of the histamine dependence of the itch. All pain behaviors, however, were left intact. These data indicate that the gastrin-releasing peptide receptor-expressing neurons are essential for itch transmission.

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

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