targeted-toxins

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)

Mu D, Sun Y-G (2017) Itch induces conditioned place aversion in mice. Neuroscience Letters 658:91-96.. doi: 10.1016/j.neulet.2017.08.046

Summary: Consistently, ablation of itch‐specific neurons that express gastrin‐releasing peptide receptor in the spinal cord also abolished itch‐induced Conditioned Place Aversion (CPA), confirming that itch‐induced CPA is dependent on the spinal itch circuit.

Usage: Mice were given a single intrathecal injection (400 ng/5 μl each) of Bombesin-SAP (Cat. #IT-40) or Control Blank-SAP (Cat. #IT-21).

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

Murtazina AR, Dilmukhametova LK, Nikishina YO, Sapronova AY, Volina EV, Ugrumov MV (2017) Changes in the secretory activity of organs producing noradrenaline upon inhibition of its synthesis in neonatal rat brain. Russ J Dev Biol 48:295-300.. doi: 10.1134/S1062360417050058

Summary: This study demonstrates that synthesis of noradrenaline after destruction of noradrenergic neurons was switched off by stereotactically injecting Anti-DBH-SAP (0.5 μg/2 μL; Cat #IT-03) into the lateral brain ventricle of neonatal rats. Forty-eight hours after treatment, expression of the tyrosine hydroxylase (TH) gene in the brain was 56% higher, 53% higher in the adrenal glands, and 55.8% higher in the organ of Zuckerkandl as compared to control (2 μL of 0.9% NaCl).

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

Challet E (2017) Circadian aspects of adipokine regulation in rodents. Best Practice & Research Clinical Endocrinology & Metabolism 31:573-582. doi: 10.1016/j.beem.2017.09.003

Summary: This paper reviews reciprocal links between the circadian clocks and rhythmic secretion of leptin, and discusses the metabolic impact of circadian desynchronization and altered rhythmic leptin.  The authors report that leptin is well-known to modulate the timing of food intake by its anorectic effects mostly mediated by the arcuate nuclei of the hypothalamus.  They cite a report by Li et al. demonstrating damage to the arcuate neurons expressing leptin receptors by local injections of Leptin-SAP (Cat. #IT-47) leads to hyperphagia coupled to arrhythmic pattern of feeding.

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

See Also:

• Li AJ et al. Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302(11):R1313-26, 2012.

Capone E, Giansanti F, Ponziani S, Lamolinara A, Iezzi M, Cimini A, Angelucci F, Sorda R, Laurenzi V, Natali PG, Ippoliti R, Iacobelli S, Sala G (2017) EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma. Oncotarget 8(56):95412-95424. doi: 10.18632/oncotarget.20728 PMID: 29221137

Objective: Using EV20 (Anti-Her3)-SAP to target Her3 positive melanoma

Summary: Linking a humanized monoclonal antibody targeting Her3, named EV20, to saporin creates a powerful cytotoxic agent targeting melanoma – which overexpress the Her3 receptor. The antibody, EV20, rapidly is internalized by Her3 whether its dependent ligand is there or not. EV20-SAP demonstrated potent and specific cytotoxicity towards human melanoma cells.

Usage: At a concentration of 19 nM only 10% of the human melanoma cells 9 (SK-MEL24 melanoma cells) survived, where free saporin at the same concentration shows no/minimal cytotoxicity.

Related Products: Saporin (Cat. #PR-01)

Echeverry S, Shi XQ, Yang M, Huang H, Wu Y, Lorenzo L-E, Perez-Sanchez J, Bonin RP, De Koninck Y, Zhang J (2017) Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801.. doi: 10.1097/j.pain.0000000000000982

Summary: Selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac-1-SAP and blockade of brain derived neurotrophic factor–TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity.  To selectively deplete microglia in the spinal cord, Mac-1-SAP was injected intrathecally.  In each group, rats received either an intrathecal injection of 12 mg/7 mL of Mac-1-SAP (n = 6-8) or equal volume of 0.9% saline (n 5 6) or the inactive unconjugated toxin, Saporin (n = 6).)

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Nichols NL, Craig TA, Tanner MA (2018) Phrenic long-term facilitation following intrapleural CTB-SAP-induced respiratory motor neuron death. Respir Physiol Neurobiol 256:43-49. doi: 10.1016/j.resp.2017.08.003

Objective: To study the impact of respiratory motor neuron death.

Summary: Intrapleural CTB-SAP mimics aspects of ALS. Seven days of CTB-SAP enhances respiratory plasticity.

Usage: Bilateral intrapleural injections of: 1) CTB-SAP (25 μg), or 2) unconjugated CTB and SAP (control).

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)

Challet E, Kalsbeek A (2017) Editorial: Circadian Rhythms and Metabolism. Front Endocrinol (Lausanne) 8:201. doi: 10.3389/fendo.2017.00201

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

Weisshaar CL, Kras JV, Pall PS, Kartha S, Winkelstein BA (2017) Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters. Neurosci Lett 655:82-89. doi: 10.1016/j.neulet.2017.07.006 PMID: 28689926

Objective: To investigate the role of peptidergic afferents in the development and maintenance of mechanical hyperalgesia, dysregulated nociceptive signaling, and spinal hyperexcitability that develop after mechanical injury to the facet joint

Summary: Isolectin-B4 saporin (IB4- SAP) was injected into the facet joint to ablate non-peptidergic cells, and the facet joint later underwent a ligament stretch known to induce pain. Administering IB4-SAP prior to a painful injury prevented the development of mechanical hyperalgesia that is typically present. Intra-articular IB4-SAP also prevented the upregulation of the glutamate transporters GLT-1 and EAAC1 in the ventral posterolateral nucleus of the thalamus and reduced thalamic neuronal hyperexcitability at day 7.

Usage: Rats received a bilateral intra-articular injections of 5µg in the C6/C7 facet joints of IB4-SAP (5 µg, IT-10) in 10μL of PBS to ablate the IB4-binding neurons. Saporin (PR-01) was used as control.

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

Alam M, McGinty D (2017) Acute effects of alcohol on sleep are mediated by components of homeostatic sleep regulatory system: An Editorial Highlight for ‘Lesions of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption’ on page 710. J Neurochem 142(5):620-623.. doi: 10.1111/jnc.14100

Summary: In the study published in 2017, Sharma and colleagues report that the wake-promoting BF cholinergic neurons are critically involved in the acute alcohol-induced sleep promoting response and that extracellular adenosine buildup in the BF mediates this response. Using 192-IgG-SAP (Cat. #IT-01), they ablated BF cholinergic neurons unilaterally and compared extracellular adenosine levels on lesioned versus non-lesioned sides after local delivery of alcohol via reverse microdialysis. They found that adenosine levels were significantly lower (nearly 50%) on the side with a loss of cholinergic neurons.

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

See Also:

• Sharma R et al. Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption. J Neurochem 142:710-720, 2017.