Targeting Topics 12q2

IB4-saporin attenuates acute and eliminates chronic muscle pain in the rat.

Alvarez P, Gear RW, Green PG, Levine JD.

Exp Neurol 233(2):859-865, 2012.

In order to clarify the roles of isolectin B4-positive and IB4-negative nociceptors in inflammatory and ergonomic muscle pain, the authors administered 3.2 µg of IB4-SAP (Cat. #IT-10) into the intrathecal space of rats. Although the baseline mechanical nociceptive threshold was not affected in the lesioned animals, mechanical hyperalgesia had a shorter duration. In the ergonomic models peak hyperalgesia was attenuated, and prolongation of PGE2-induced mechanical hyperalgesia was completely prevented.

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry.

Asano Y.

J Histochem Cytochem 60(3):229-242, 2012.

The mammalian ovary engages in continuous growth and cellular differentiation as long as the animal is capable of reproduction. During these processes iron ions are released from heme structures; these ions are capable of generating free radicals. The purpose of this study was to investigate non-heme iron distribution in ovarian tissue, and how this distribution changes during aging. Lipid peroxidation was monitored by immunohistochemistry using anti-conjugated malondialdehyde (Cat. #AB-T090). The data indicate that increasing oxidative stress, non-heme iron accumulation in ovarian stromal tissue, and aging are related.

Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn.

Choi JI, Koehrn FJ, Sorkin LS.

Mol Pain 8(1):4, 2012.

In this work the authors administered 100 ng SSP-SAP (Cat. #IT-11) into the intrathecal space of rats (saporin, Cat. #PR-01, was used as a control). Lesioned animals displayed decreased carrageenan-induced mechanical allodynia, and carrageenan-induced phosphorylation of Akt was blocked throughout the spinal cord gray matter. Anti-NK-1 (Cat. #AB-N33AP) was used for immunohistochemistry.

Cholinergic modulation of a specific memory function of prefrontal cortex.

Croxson PL, Kyriazis DA, Baxter MG.

Nat Neurosci 14(12):1510-1512, 2011.

The authors investigated loss of acetylcholine in the large and highly differentiated PFC’s of rhesus monkeys. The monkeys received 80-92 20-ng injections of ME20.4-SAP (Cat. #IT-15) per hemisphere. Lesioned animals were severely impaired on tasks involving spatial working memory.

Two patterns of thrombopoietin signaling suggest no coupling between platelet production and thrombopoietin reactivity in thrombocytopenia-absent radii syndrome.

Fiedler J, Strauss G, Wannack M, Schwiebert S, Seidel K, Henning K, Klopocki E, Schmugge M, Gaedicke G, Schulze H.

Haematologica 97(1):73-81, 2012.

Lower than normal blood platelet counts result from a congenital disorder called thrombocytopenia (thrombocytopenia absent radii syndrome, or TAR). Recent work indicates a complex pattern of inheritance, and possibly that TAR is at least a digenic disorder. The authors performed an extended study investigating signal transduction via immunoblotting, gel electrophoretic shift assays, and flow cytometry. One of the antibodies used was anti-p70 S6K (Cat. #AB-241). The authors conclude that there are defects in both platelet production and function in TAR.

Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

Gibbons DD, Southerland EM, Hoover DB, Beaumont E, Armour JA, Ardell JL.

Am J Physiol Regul Integr Comp Physiol 302(3):R357-64, 2012.

Cardiac arrhythmias can be generated by excessive activation of specific inputs to the intrinsic cardiac nervous system. The authors sought to determine whether subpopulations of neurons were responsible for this activation, and therefore potential therapeutic targets. A series of studies were done following electrical stimuli to the mediastinal nerves. Choline acetyltransferase levels were assessed using anti-ChAT (Cat. #AB-N34) in immunohistochemistry. The data suggest activation of certain neurons by mediastinal nerve stimulation results in atrial arrhythmias leading to atrial fibrillation.

Spinal bombesin-recognized neurones mediate more nonhistaminergic than histaminergic sensation of itch in mice.

Han N, Zu JY, Chai J.

Clin Exp Dermatol 37(3):290-295, 2012.

The authors administered 400 ng of Bombesin-SAP (Cat. #IT-40) to the lumbar spinal subarachnoid space of rats and evaluated the distribution of Fos-positive cells in the dorsal horn after stimulation. Saporin (Cat. #PR-01) was used as a control. The results demonstrate that the neurons eliminated by Bombesin-SAP are critical to both acute and chronic itch pathways, although they have more effect on nonhistaminergic sensation.

Selective cholinergic depletion in medial septum leads to impaired long term potentiation and glutamatergic synaptic currents in the hippocampus.

Kanju PM, Parameshwaran K, Sims-Robinson C, Uthayathas S, Josephson EM, Rajakumar N, Dhanasekaran M, Suppiramaniam V.

PLoS One 7(2):e31073, 2012.

Long term potentiation (LTP) is dependent on excitatory neurotransmission in the hippocampus, which plays a major role in learning and memory. The authors examine whether cholinergic lesions in the medial septum result in LTP alteration or affect synaptic glutamate receptor subtypes. After bilateral administration of 192-IgG-SAP (Cat. #IT-01, 50 ng per injection) into the medial septum of rats, hippocampal slices were made and the LTP of the slices was measured. The data show modulation of medial septal LTP and hippocampal glutaminergic currents by cholinergic afferents.

Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug.

Selbo PK, Weyergang A, Eng MS, Bostad M, Maelandsmo GM, Hogset A, Berg K.

J Control Release 159(2):197-203, 2012.

Many anti-cancer drugs are substrates of the ATP-binding cassette transporter ABCG2. Unfortunately ABCG2 is also thought to play an important role in multi-drug resistance and the protection of cancer stem cells against chemotherapeutics and photodynamic therapy. This paper examined whether photosensitizers used in photochemical internalization (PCI) are substrates for ABCG2. Streptavidin-ZAP (Cat. #IT-27) was combined with biotinylated EGF and applied to cells in culture; saporin (Cat. #PR-01) was used as a control. The data show that PCI with the EGF-saporin toxin did not utilize ABCG2 to enter cells.

A Pivotal Role of Lumbar Spinothalamic Cells in the Regulation of Ejaculation via Intraspinal Connections.

Staudt MD, Truitt WA, McKenna KE, de Oliveira CV, Lehman MN, Coolen LM.

J Sex Med 9(9):2256-2265, 2012.

The authors examined the hypothesis that specific lumbar spinothalamic (LSt) cells control ejaculation through intraspinal connections. Rats received six bilateral injections of SSP-SAP (Cat. #IT-11) into the spinal cord, 48 ng in total. Saporin (Cat. #PR-01) was used as a control. It was found that while erectile function and emission were not affected, the usual rhythmic contractions of the bulbocaveronosus muscle during ejaculation were prevented.

Subplate neurons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex.

Tolner EA, Sheikh A, Yukin AY, Kaila K, Kanold PO.

J Neurosci 32(2):692-702, 2012.

Immature cortices in both human and rat have spontaneous activity associated with the maturation of cortical synapses and neuronal circuits. In order to investigate what cells are controlling these events the authors administered 400 ng of 192-IgG-SAP (Cat. #IT-01) to the S1 cortex hindlimb/forelimb area of rats. mu p75-SAP (Cat. #IT-16) and mouse-IgG-SAP (Cat. #IT-18) were used as controls. This lesion eliminates subplate neurons which results in a significant loss of evoked spindle burst activity.

Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation.

Zhang L, Hadley GA.

Chin Med J (Engl) 123(24):3644-3651, 2010.

This work investigates whether depletion of CD103-positive cells protects transplanted islets from host-immune cell attack. Diabetes was induced in mice, followed by an islet transplant. Anti-CD103-SAP (Cat. #IT-50) was administered via i.p. injection (1.0 mg/kg or 2.0 mg/kg). Rat IgG-SAP (Cat. #IT-17) was used as a control. Diabetic mice treated with anti-CD103-SAP after islet transplantation had an indefinite survival time as compared to untreated mice that survived fewer than 20 days.