Targeting Topics 13q3

Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.

Liu Y, Weick JP, Liu H, Krencik R, Zhang X, Ma L, Zhou GM, Ayala M, Zhang SC.

Nat Biotechnol 31(5):440-447, 2013.

Progenitor cells were transplanted into mice that had received 1.5 μg of mu p75-SAP (Cat. #IT-16) into the medial septum. See cover article in Targeting Trends 14(3).

The cells and circuitry for itch responses in mice.

Mishra SK, Hoon MA.

Science 340(6135):968-971, 2013.

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.

A Novel Model for Evaluating Therapies Targeting Human Tumor Vasculature and Human Cancer Stem-like Cells.

Burgos-Ojeda D, McLean K, Bai S, Pulaski H, Gong Y, Silva I, Skorecki K, Tzukerman M, Buckanovich RJ.

Cancer Res 73(12):3555-3565, 2013.

Targeting tumor vascular markers (TVM) is difficult since the vasculature expression profile of tumor types tends to be very different. The authors established a human embryonic stem cell-derived teratoma and tested it as a model for TVM expression by challenging primary human MSCs in vitro and in an in vivo mouse tumor model created with anti-human Thy1 plus Streptavidin-ZAP (Cat. #IT-27).

Striatal patch compartment lesions alter methamphetamine-induced behavior and immediate early gene expression in the striatum, substantia nigra and frontal cortex.

Murray RC, Gilbert YE, Logan AS, Hebbard JC, Horner KA.

Brain Struct Funct Epub2013.

In this work, the authors investigated the function of the patch compartment in abnormally repetitive motor actions (stereotypy) in response to a psychostimulant such as methampheta-mine (meth). Rats received bilateral injections of Dermorphin-SAP (Cat. #IT-12; 17 ng) into the rostral striatum. When treated with meth, lesioned animals displayed reduced stereotypy, increased motor activity, and enhanced c-Fos expression.

Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.

Bostad M, Berg K, Hogset A, Skarpen E, Stenmark H, Selbo PK.

J Control Release 168(3):317-326, 2013.

Targeted therapies for cancer can be trapped in the lysosome and compartmentalized away from the target. Photochemical internalization is a method to increase the efficacy of these compounds by releasing the therapeutic portion of the molecule from the endocytic vesicles to the cytosol by the use of light. The authors demonstrate this method on cells expressing the cancer stem cell marker CD133. Biotinylated antibodies against CD133 were combined with Streptavidin-ZAP (Cat. #IT-27) and applied to cell lines.

Cortical cholinergic input is required for normal auditory perception and experience-dependent plasticity in adult ferrets.

Leach ND, Nodal FR, Cordery PM, King AJ, Bajo VM.

J Neurosci 33(15):6659-6671, 2013.

In order to study how cholinergic input from the nucleus basalis affects auditory perception and learning, the authors injected a total of 35.2 ng of ME20.4-SAP (Cat. #IT-15) into the nucleus basalis in each hemisphere of ferrets. Based on several learning tasks, the data suggest that these cholinergic inputs aid in the perception of sound source location and aid in the adaptation of the auditory system to changes in spatial cues.

Cutting Edge: memory regulatory t cells require IL-7 and not IL-2 for their maintenance in peripheral tissues.

Gratz IK, Truong HA, Yang SH, Maurano MM, Lee K, Abbas AK, Rosenblum MD.

J Immunol 190(9):4483-4487, 2013.

Recently a new class of regulatory T cells (mTregs) were found that persist in non-lymphoid tissues and are involved in suppressing autoimmune responses. In order to examine the roles that IL-2 and IL-7 play in the development and regulation of mTregs, the authors used genetic deletion, adoptive T-cell transfer, and in vivo neutralization techniques. 5 μg of intravenous OX7-SAP (Cat. #IT-02) per mouse was used to deplete CD90.1-positive cells during the adoptive transfer experiment. It was found that IL-7 is essential for the steady-state maintenance of mTregs in skin.

Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type.

Rust S, Guillard S, Sachsenmeier K, Hay C, Davidson M, Karlsson A, Karlsson R, Brand E, Lowne D, Elvin J, Flynn M, Kurosawa G, Hollingsworth R, Jermutus L, Minter R.

Mol Cancer 12:11, 2013.

The authors investigated a phenotypic antibody screening technique, in which antibodies are selected by function rather than target specificity. One facet of the screening procedure for hybridomas generated using a cancer cell line as antigen was the use of Mab-ZAP (Cat. #IT-04) to assess cell binding and internalization.

Immunolesion-induced loss of cholinergic projection neurons promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice.

Hartig W, Saul A, Kacza J, Grosche J, Goldhammer S, Michalski D, Wirths O.

Neuropathol Appl Neurobiol Epub2013.

3xTg transgenic mice were treated with 2 μg of mu p75-SAP (Cat. #IT-16) into the right lateral ventricle to eliminate cholinergic neurons in the basal forebrain. These mice already have age-dependent β-amyloidosis and tau hyperphosphorylation. This new model supplies a potential framework in which to study the entire pathology of Alzheimer’s disease.

Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.

Lelkes Z, Porkka-Heiskanen T, Stenberg D.

J Sleep Res Epub2013.

Wakefulness is enhanced by the injection of noradrenaline into the basal forebrain, but it has not been clear whether cholinergic or non-cholinergic neurons are involved. 230 ng of 192-IgG-SAP (Cat. #IT-01) was administered to the horizontal diagonal band/substantia innominata/ magnocellular preoptic nucleus of rats. Upon treatment with methoxamine, lesioned animals lost the non-REM sleep-suppressing effect, but the REM sleep-suppressing effect remained intact.

An environment-dependent modulation of cortical neural response by forebrain cholinergic neurons in awake rat.

Ariffin MZ, Chang LS, Koh HC, Low CM, Khanna S.

Brain Res 1513:72-84, 2013.

Rats received 168 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum and induction of c-Fos expression in response to either familiar or novel stimuli was measured.

Plasmin induces intercellular adhesion molecule 1 expression in human endothelial cells via nuclear factor-kappaB/mitogen-activated protein kinases-dependent pathways.

Li Q, Syrovets T, Simmet T, Ding J, Xu J, Chen W, Zhu D, Gao P.

Exp Biol Med (Maywood) 238(2):176-186, 2013.

Intracellular adhesion molecule 1 (ICAM-1) mediates inflammatory cell migration – an early step in atherosclerosis. The authors investigated an inflammatory cascade activated by plasmin using a variety of methods, including flow cytometry with anti-mouse IgG-FITC (Cat. #FL-07) and anti-rabbit IgG-FITC (Cat. #FL-04).

Evaluating the Role of Neuronal Nitric Oxide Synthase-Containing Striatal Interneurons in Methamphetamine-Induced Dopamine Neurotoxicity.

Fricks-Gleason AN, Keefe KA.

Neurotox Res 24(2):288-297, 2013.

Using the fact that neuronal nitric oxide synthase (nNOS)-containing neurons in the striatum express the substance P receptor, the authors injected four locations in the striatum with 3 ng each of SSP-SAP (Cat. #IT-11). Blank-SAP (Cat. #IT-21) was used as a control. Although there was a significant loss of nNOS-containing neurons, the lesions did not attenuate NO production.

The role of visual cortex acetylcholine in learning to discriminate temporally modulated visual stimuli.

Minces VH, Alexander AS, Datlow M, Alfonso SI, Chiba AA.

Front Behav Neurosci 7:16, 2013.

In order to examine some of the minor differences in the temporal structure of stimuli, the authors bilaterally injected 37.5 ng of 192-IgG-SAP (Cat. #IT-01) between the lambda and bregma of rats. This injection reduced acetylcholine projections to the visual cortex. Loss of that cholinergic input impaired the ability of the lesioned animals to perform fine discriminations, but previously learned discriminations remained unimpaired.

Photochemical internalization of CD133-targeting immunotoxins efficiently depletes sarcoma cells with stem-like properties and reduces tumorigenicity.

Stratford EW, Bostad M, Castro R, Skarpen E, Berg K, Hogset A, Myklebost O, Selbo PK.

Biochim Biophys Acta 1830(8):4235-4243, 2013.

In this work the authors used photochemical internalization (PCI) to facilitate local cytosolic toxin release from various biotinylated-anti-CD133 antibodies coupled with Streptavidin-ZAP (Cat. #IT-27) in SW872 cells. This technique demonstrates potential for non-invasive sarcoma therapy.

Combinatorial Treatment of Tart Cherry Extract and Essential Fatty Acids Reduces Cognitive Impairments and Inflammation in the mu-p75 Saporin-Induced Mouse Model of Alzheimer’s Disease.

Matchynski JJ, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL.

J Med Food 16(4):288-295, 2013.

The authors investigated the efficacy of a combinatorial therapy, Cerise Total-Body Rhythm (TBR) by treating mice with TBR prior to and following icv administration of 0.8 μg of mu p75-SAP (Cat. #IT-16).

BB2 bombesin receptor-expressing spinal neurons transmit herpes-associated itch by BB2 receptor-independent signaling.

Sasaki A, Adhikari S, Andoh T, Kuraishi Y.

Neuroreport Epub2013.

Using a skin rash model created by inoculating mice with human herpes virus, bombesin receptor-expressing spinal neurons were lesioned intrathecally with 400 ng of Bombesin-SAP (Cat. #IT-40). Lesioned animals displayed reduced scratching, but licking (due to pain) was not reduced.

Time Course Study of Targeted Ablation of KNDy Neurons, but not Tyrosine-Hydroxylase Neurons, in the Rat Arcuate Nucleus Using a Neurokinin B-Saporin.

Helena CV, Kalil B, Anselmo-Franci JA, Bertram R.

Endocr Rev 34 (03_MeetingAbstracts):OR47-5, 2013.

Ovariectomized rats were given bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus for a time course study of KNDy neuron loss. Blank-SAP (Cat. #IT-21) was used as a control.

State-dependent contribution of the hyperpolarization-activated na+/k+ and persistent na+ currents to respiratory rhythmogenesis in vivo.

Montandon G, Horner RL.

J Neurosci 33(20):8716-8728, 2013.

The hyperpolarization-activated cation current in the preBötzinger complex (preBötC) was identified as a critical component of respiratory rhythm. An anti-neurokinin 1 receptor antibody (Cat. #AB-N04 replaced by Cat. #AB-N33AP) at a 1:1000 dilution was used to identify preBötC neurons in the brainstem.