Targeting Topics 11q1

The cell surface structure of Tumor Endothelial Marker 8 (TEM8) is regulated by the actin cytoskeleton

Yang MY, Chaudhary A, Seaman S, Dunty J, Stevens J, Elzarrad MK, Frankel AE, St Croix B

Biochim Biophys Acta 1813(1):39-49, 2011.

Tumor endothelial marker 8 (TEM8) is a cell surface protein that is up-regulated on tumor blood vessels. Overexpression of this protein, however, produces a form that is not recognized by the SB5 monoclonal antibody used to bind TEM8. While cells expressing normal levels of TEM8 were killed by an application of biotinylated SB5 plus either 1 nM or 10 nM streptavidin-ZAP (Cat. #IT-27), cells overexpressing the protein did not bind the immunotoxin. Understanding the structural differences between the two forms of TEM8 will help in the design of therapeutic antibodies against these tumor cells.

Intrinsically photosensitive retinal ganglion cells

Do MTH, Yau K

Physiol Rev 90(4):1547-1581, 2010.

This review presents recent data that has established the importance of intrinsically photosensitive retinal ganglion cells (ipRPG) in nonimage visual functions. The use of melanopsin-SAP (Cat. #IT-44) in mice is discussed. It is of note that depletion of ipRPG’s using melanopsin-SAP resulted in deficits in communication to nonimage regions of the brain, but image vision appeared normal.

Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice

Lyons AM, Thiele TE

Peptides 31(12):2193-2199, 2010.

Neuropeptide Y (NPY) in the hypothalamus is known to modulate feeding behavior. In this work the authors used bilateral 48-ng injections of NPY-SAP (Cat. #IT-28) into the central amygdala or basomedial hypothalamus (BMH) of rats to investigate the role of NPY in anxiety. Blank-SAP (Cat. #IT-21) was used as a control. Injections into the amygdala increased anxiety-like behavior, while injections into the BMH reduced anxiety-like behavior. BMH injections also initiated an increase of NPY-1 receptor expression in the basolateral nuclei of the amygdala.

Targeted delivery of saporin toxin by monoclonal antibody to the transcobalamin receptor, TCblR/CD320

Quadros EV, Nakayama Y, Sequeira JM

Mol Cancer Ther 9(11):3033-3040, 2010.

Vitamin B12 is necessary for cell proliferation. Cancer cells display an increased expression of TCb1R, the receptor that facilitates the intake of B12. In order to evaluate the potential of using immunotoxins to eliminate cancer cells expressing TCb1R the authors performed a series of in vitro experiments using their monoclonal antibody plus Mab-ZAP (Cat. #IT-04) in varying concentrations. The results indicate that this is a viable therapeutic model that causes minimal peripheral damage.

Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment

Gompf HS, Mathai C, Fuller PM, Wood DA, Pedersen NP, Saper CB, Lu J

J Neurosci 30(43):14543-14551, 2010.

Locus ceruleus (LC) activity is strongly associated with wakefulness. In this work the authors examined arousal due to environmental stimuli after lesioning of the LC. Injections of 0.25-1 µg of Anti-DBH-SAP (Cat. #IT-03) were administered into the lateral ventricle of rats. Lesioned animals did not show sustained neurobehavioral and EEG arousal in response to a novel environment. The data suggest sustained attention requires an interaction between the LC and the anterior cingulate cortex.

Developmental origin of preBötzinger Complex respiratory neurons

Gray PA, Hayes JA, Ling GY, Llona I, Tupal S, Picardo MCD, Ross SE, Hirata T, Corbin JG, Eugenín J, Del Negro CA

J Neurosci 30(44):14883-14895, 2010.

Breathing in adult rats requires a subset of neurons in the preBötzinger Complex (preBötC) that express the neurokinin-1 receptor and the peptide somatostatin. In this work the authors investigate the developmental origins of these cells. Using various techniques, including immunohistochemistry with a neurokinin-1 receptor antibody (Cat. #AB-N04; product in re-development), it is demonstrated that neurons derived from Dbx-1-expressing progenitor cells are important in the generation of respiratory behavior.

Cerebellar modules: individual or composite entities?

Cerminara NL

J Neurosci 30(48):16065-16067, 2010.

This short review discusses the compartmentalization of cerebellar modules. Much research has been done to associate particular motor control functions with particular modules. Chemical lesioning is an inadequate technique because the lesion is non-specific. The use of CTB-SAP (Cat. #IT-14) to affect the function of a single module is discussed.

The effects of neonatal forebrain cholinergic lesion on adult hippocampal neurogenesis

Rennie K, Fréchette M, Pappas BA

Brain Res 1373:79-90, 2011.

Intraventricular injections of 192-IgG-SAP (Cat. #IT-01) have been shown to reduce the number of cells expressing a marker for immature neuroblasts in the dentate gyrus, as well as possibly impairing the response to environmental enrichment. This study looked to expand on those observations. Infusion of 300 ng of 192-IgG-SAP was delivered into each ventricle of post-natal, Day 7 rats. The data suggest that the lesion accelerates the death of new cells, but does not affect survival rate or phenotypic differentiation.

Acetylcholine and attention

Klinkenberg I, Sambeth A, Blökland A

Behav Brain Res 221(2):430-442, 2011.

This review article summarizes studies investigating the role of acetylcholine in attention and cognition. The roles of 192-IgG-SAP (Cat. #IT-01) and mu p75-SAP (Cat. #IT-16) in these experiments are discussed. Acetylcholine is thought to play a top-down role in the prefrontal, parietal, and somatosensory regions; playing an important role in the control of attentional-orienting and stimulus discrimination.

Spatial memory alterations by activation of septal 5HT(1A) receptors: no implication of cholinergic septohippocampal neurons

Koenig J, Lecourtier L, Cosquer B, Pereira PM, Cassel J

Psychopharmacology (Berl) 214(2):437-454, 2011.

These experiments examined what effect damaged cholinergic neurons would have on memory deficits induced by the 5-HT1A/5-HT7 receptor agonist 8-OH-DPAT. Rats received 0.4-µg injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, delivered through an infusion device. Through use of a water maze test, the authors show that several neuronal populations are involved in processing hippocampal information, and non-cholinergic neurons in this region may be more important than the cholinergic ones for memory processing.

Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats

Di Sebastiano AR, Wilson-Pérez HE, Lehman MN, Coolen LM

Horm Behav 59(1):1-8, 2011.

The neuropeptide orexin is important in the feedback mechanisms of food intake and drugs of abuse. This work investigates the role of orexin in sexual reward in male rats. Two 200-ng bilateral hypothalamic injections of orexin-SAP (Cat. #IT-20; discontinued) were made into each hemisphere. Blank-SAP (Cat. #IT-21) was used as a control. Although it was shown orexin neurons are activated by sexual reward cues, the data suggest that orexin is not essential for sexual performance and motivation.

Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation

Gil-Bea FJ, Solas M, Mateos L, Winblad B, Ramírez MJ, Cedazo-Mínguez A

Hippocampus Epub June, 2010.

The authors investigated the role of activity-regulated cytoskeleton associated protein (Arc) and brain-derived neurotrophic factor (BDNF) in cholinergic-induced memory formation. Rats received 67-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the third ventricle after behavioral training. Lesioned animals had decreased protein and mRNA for both Arc and BDNF. Memory acquisition and recovery of acquisition were both affected. The data indicate that cholinergic denervation of the hippocampus affects the muscarinic facets of spatial memory acquisition.

Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: Effects on proactive interference

Pang KCH, Jiao X, Sinha S, Beck KD, Servatius RJ

Hippocampus 21(8):835-846, 2011.

Recent work implicates the medial septum (MS) and diagonal band (DB) in the control of proactive interference — forgetting older information when learning new information. Rats received GAT1-SAP (Cat. #IT-32) injections into the MS and the DB (162.5 ng and 130 ng, respectively; the DB injections were bilateral). The results parallel other studies using 192-IgG-SAP (Cat. #IT-01) and other toxins, reinforcing the indications that GABAergic MSDB neurons are an integral part of proactive interference control.

Cholinergic depletion in the nucleus accumbens: Effects on amphetamine response and sensorimotor gating

Laplante F, Lappi DA, Sullivan RM

Prog Neuropsychopharmacol Biol Psychiatry 35(2):501-509, 2011.

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 observed in schizophrenia.