2011 Targeting Trends Review

Wilkinson KA, Fu Z, Powell FL (2011) Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats. Am J Physiol Regul Integr Comp Physiol 301(2):R343-R350. doi: 10.1152/ajpregu.00375.2010

Summary: Interaction of the multiple brainstem areas that have been established as CO2-sensitive is not well understood. In order to investigate chemoreceptor roles in the nucleus tractus solitarii (NTS) the authors injected 2.6 ng of SP-SAP (alternative: SSP-SAP; Cat. #IT-11) into the caudal NTS of rats. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate that neurokinin-1 receptor-expressing cells in the NTS contribute to plasticity during chronic hypoxia.

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

Antonini V, Marrazzo A, Kleiner G, Coradazzi M, Ronsisvalle S, Prezzavento O, Ronsisvalle G, Leanza G (2011) Anti-amnesic and neuroprotective actions of the sigma-1 receptor agonist (-)-MR22 in rats with selective cholinergic lesion and amyloid infusion. J Alzheimers Dis 24(3):569-586. doi: 10.3233/JAD-2011-101794 PMID: 21297260

Summary: Sigma-1 receptor agonists such as (-)-MR22 are potential therapeutic drugs for the treatment of cognitive and affective disorders. To model a cognitive disorder, rats received 81-ng bilateral injections of 192- IgG-SAP (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band of Broca, and 130-ng bilateral injections into the nucleus basalis magnocellularis. Lesioned animals also were treated with pre- aggregated amyloid peptide. Pretreatment with (-)-MR22 reversed cognitive impairments in the double-lesioned animals, indicating the potential use of sigma-1 receptor agonists as protective agents.

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

Tai SK, Ma J, Ossenkopp KP, Leung LS (2012) Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulation. Hippocampus 22(4):914-925 . doi: 10.1002/hipo.20955

Summary: The vestibular system is highly involved with spatial navigation and memory. It is thought that modulation of hippocampal function by the vestibular system is mediated by a hippocampal theta rhythm. Rats received 140 ng of 192-IgG-SAP (Cat. #IT-01) infused into the medial septum, followed by measurement of hippocampal EEG’s and evoked potentials. Theta was attenuated in rats receiving the lesion, as well as other changes that suggest the importance of septohippocampal cholinergic activity in sensorimotor processing and spatial memory.

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

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)

Hutchins BM, Kazane SA, Staflin K, Forsyth JS, Felding-Habermann B, Smider VV, Schultz PG (2011) Selective formation of covalent protein heterodimers with an unnatural amino acid. Chem Biol 18(3):299-303. doi: 10.1016/j.chembiol.2011.01.006 PMID: 21439474

Summary: This work demonstrates the creation of a variety of constructs containing specific defined conjugation sites. One use for these molecules is to create homogenous antibody conjugates‚ meaning the properties of these conjugates can be quantitatively evaluated. Having greater control of such conjugations is essential if these types of constructs are to move toward use as therapeutics. The authors created an anti-Her2 Fab-saporin molecule and tested it in vitro. Analysis by western used anti-SAP-HRP (Cat. #AB-15-HRP) to detect the conjugated molecule.

Related Products: Saporin Goat Polyclonal, HRP-labeled (Cat. #AB-15HRP)

Chung JS, Shiue LH, Duvic M, Pandya A, Cruz PDJ, Ariizumi K (2011) Sezary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface. Blood 117(12):3382-3390. doi: 10.1182/blood-2010-08-302034

Summary: Syndecan-4 (SD-4) is a transmembrane heparan sulfate proteoglycan. The Sézary syndrome (SS) subset of cutaneous T-cell lymphoma overexpresses distinct heparan sulfate moieties, giving the authors a specific target for these cells. Biotinylated DC-HIL- Fc (the extracelluar domain of dendritic cell- associated heparan sulfate proteoglycan- integrin ligand fused to Fc of mouse IgG) was combined at a 1:1 molar ratio with streptavidin-ZAP (Cat. #IT-27). In vitro, this targeted toxin eliminated SS cells, preventing their proliferation and suggesting a method for SS treatment.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Hernandez-Melesio MA, Gonzalez-Esquivel D, Ortiz-Plata A, Sanchez-Mendoza A, Sanchez-Garcia A, Alcaraz-Zubeldia M, Rios C, Perez-Severiano F (2011) Molsidomine modulates the cNOS activity in an experimental model of cholinergic damage induced by 192-IgG saporin. Neurosci Lett 491(2):133-137. doi: 10.1016/j.neulet.2011.01.023

Summary: Nitric oxide (NO) is required for the survival of cholinergic neurons in the basal forebrain. Delivery of nerve growth factor (NGF) is related to the modulation of NO – as excessive NO can lead to excitotoxicity. The authors administered molsidomine to rats that had previously received 220 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Molsidomine is a NO donator, and produced a significant recovery of NO activity in lesioned animals, indicating a potential therapeutic pathway.

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

Heldmann U, Mine Y, Kokaia Z, Ekdahl CT, Lindvall O (2011) Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke. Exp Neurol 229(2):391-398. doi: 10.1016/j.expneurol.2011.03.005

Summary: One result of ischemic stroke is migration of newly formed neuroblasts into the injured area from the subventricular zone (SVZ). The authors investigated the role of microglia, which also accumulate in the SVZ after stroke, in this process. Rats received 5-µg or 10-µg intracerebroventricular injections of Mac-1-SAP (Cat. #IT-33) with varying schedules as to injection and sacrifice. The data indicate that the presence of microglia after stroke does not affect the number or migration of neuroblasts from the SVZ.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Takasusuki T, Yaksh TL (2011) The effects of intrathecal and systemic gabapentin on spinal substance P release. Anesth Analg 112(4):971-976. doi: 10.1213/ANE.0b013e31820f2a16 PMID: 21385982

Summary: Intrathecal or systemically-administered gabapentin is an antihyperalgesic. Given that gabapentin binds a voltage-sensitive calcium channel and that some of these channels regulate substance P (SP) release, the authors investigated whether gabapentin affects SP levels. Immunohistochemistry was done in rats following a gabapentin/formalin pain model. A neurokinin-1 receptor antibody (Cat. #AB-N04) was used to quantitate NK1r, and therefore assess SP activity. It was found that both spinal and systemic gabapentin inhibit SP release from small, primary afferents.

Related Products: Antibody to NK-1 Receptor (Cat. #AB-N04)

Sawada R, Sun SM, Wu X, Hong F, Ragupathi G, Livingston PO, Scholz WW (2011) Human monoclonal antibodies to Sialyl-Lewisa (CA19.9) with potent CDC, ADCC, and antitumor activity. Clin Cancer Res 17(5):1024-1032. doi: 10.1158/1078-0432.CCR-10-2640

Summary: In this work the authors investigated the use of a carbohydrate antigen, sialyl-Lewisa (CA19.9), as a target for cancer therapeutics. Human monoclonal antibodies were generated against CA19.9 and characterized using ELISA and flow cytometry. To assess internalization one antibody, 5B1, was combined with Hum-ZAP (Cat. #IT-22) and applied to CA19.9-expressing BxPC3 cells. The cytotoxicity of the 5B1-Hum- ZAP complex indicates that CA19.9 may be a target for cancer therapy.

Related Products: Hum-ZAP (Cat. #IT-22)