Targeting Topics 09q1

Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors

Zhang W, Gardell S, Zhang D, Xie JY, Agnes RS, Badghisi H, Hruby VJ, Rance N, Ossipov MH, Vanderah TW, Porreca F, Lai J

Brain 132(3):778-787, 2009.

It has been hypothesized that a subset of rostral ventromedial medulla (RVM) neurons co-expressing the cholecystokinin type 2 receptor and the mu-opioid receptor are responsible for the maintenance of neuropathic pain. Rats were treated with 50-ng bilateral RVM injections of Dermorphin-SAP (Cat. #IT-12), CCK-SAP (Cat. #IT-31), or saporin (Cat. #PR-01) as a control. Lesion of the RVM neurons prevented hyperalgesia in response to CCK treatment, and shortened abnormal pain states caused by sciatic nerve injury.

Cardiac Damage after Lesions of the Nucleus Tractus Solitarii

Nayate A, Moore SA, Weiss RM, Taktakishvili O, Lin LH, Talman WT

Am J Physiol Regul Integr Comp Physiol 296(2):R272-R279, 2009.

Specific neurokinin-1 (NK-1) receptor-expressing neuron lesions in the nucleus tractus solitarii (NTS) have led to the unexplained death of treated rats. In this work the authors examined cardiac specific parameters in rats after administration of 9.4 ng of SSP-SAP (Cat. #IT-11). The SSP-SAP was directed to either the dorsolateral and medial portions of the NTS, or into the brain stem outside of the NTS as a control. The data suggests that NTS lesion interrupting the baroreflex may induce cardiac arrythmias and other myocardial changes leading to sudden cardiac death.

Endosialin protein expression and therapeutic target potential in human solid tumors: sarcoma versus carcinoma

Rouleau C, Curiel M, Weber W, Smale R, Kurtzberg L, Mascarello J, Berger C, Wallar G, Bagley R, Honma N, Hasegawa K, Ishida I, Kataoka S, Thurberg BL, Mehraein K, Horten B, Miller G, Teicher BA

Clin Cancer Res 14(22):7223-7236, 2008.

Endosialin is an antigen expressed in many human cancer cell lines. As part of a wide-ranging study investigating clinical specimens, cell culture, and animal models, this group used Hum-ZAP (Cat. #IT-22) combined with a humanized anti-endosialin antibody in cell proliferation assays. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The anti-endosialin antibody and Hum-ZAP were incubated together in equimolar concentrations then applied to cells in culture in 0.5 pM to 50 nM concentrations. Various cancers, including synovial sarcoma, fibrosarcoma, and osteosarcoma among others, were found to express endosialin.

Attentional demands for demonstrating deficits following intrabasalis infusions of 192 IgG-saporin

Burk JA, Lowder MW, Altemose KE

Behav Brain Res 195(2):231-238, 2008.

Attentional processing has been shown to be dependent on basal forebrain cholinergic inputs to the cerebral cortex. In this work the authors wished to specify which components should be used to demonstrate deficits following the loss of these neurons. Rats received 200 ng intrabasalis infusions of 192-IgG-SAP (Cat. #IT-01). Testing of lesioned animals indicated that attentional deficits are due to increase of overall attentional task demands as opposed to any single task parameter.

Organization of food protection behavior is differentially influenced by 192 IgG-saporin lesions of either the medial septum or the nucleus basalis magnocellularis

Martin MM, Winter SS, Cheatwood JL, Carter LA, Jones JL, Weathered SL, Wagner SJ, Wallace DG

Brain Res 1241:122-135, 2008.

In this work the authors used a food-protection model to investigate the role of cholinergic neurons in the processing of information from internal and external sources. Rats received the following amounts of 192-IgG-SAP (Cat. #IT-01): 15 ng or 20 ng into the medial septum (MS), or 20 ng into the nucleus basalis magnocellularis (NB). While the NB lesions reduced the number of successful food protection behaviors, lesions in the MS disrupted the temporal organization of this behavior.

Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy

Fitz NF, Gibbs RB, Johnson DA

Brain Res Bull 77(6):356-360, 2008.

It has been theorized that the effect of cholinergic lesions of the medial septum on learning depend on the stressful nature of the task being learned. The authors injected 0.2 µg of 192-IgG-SAP (Cat. #IT-01) into the medial septum of rats, then examined the strategies used by these animals to learn a delayed matching to position T-maze task. Lesioned animals were less able to switch from one strategy to another, indicating that this mechanism is the primary one affected by septal cholinergic lesions.

Selective lesion of medial septal cholinergic neurons followed by a mini-stroke impairs spatial learning in rats

Craig LA, Hong NS, Kopp J, McDonald RJ

Exp Brain Res 193(1):29-42, 2009.

Recent work has suggested that reduced levels of acetylcholine, seen in Alzheimer’s disease patients, increases the susceptibility of hippocampal neurons to future challenges. Rats received two injections totaling 7.5 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band of Broca. The vasoconstrictor endothelin-1 was used to create small localized strokes in the hippocampus of lesioned animals. The data suggest that loss of these hippocampal neurons compromises functional recovery from stroke.

Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin

Bee LA, Dickenson AH

Pain 140(1):209-223, 2008.

Rostral ventromedial medulla (RVM) facilitatory On cells are thought to be involved in the mechanisms that control chronic pain. Dermorphin-SAP (Cat. #IT-12, 3 pmol) injected into the RVM of rats was used to examine how mu-opioid receptor-expressing facilitatory cells fit into this circuit. Saporin (Cat. #PR-01) was used as a control. The results show that activity in the RVM may influence the outcome of nerve injury.

The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions

Kalinchuk AV, McCarley RW, Stenberg D, Porkka-Heiskanen T, Basheer R

Neuroscience 157(1):238-253, 2008.

The level of adenosine in the basal forebrain increases during sleep deprivation (SD). The cholinergic system of the basal forebrain is thought to be involved in the control of this process. 0.23 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the horizontal diagonal band/ substantia innominata/ magnocellular preoptic nucleus, or 6 µg into the lateral ventricle of rats. The time course was dependent on the injection site, but eventually the SD-induced increase in adenosine was virtually eliminated.

Cholinergic depletion of the medial septum followed by phase shifting does not impair memory or rest-activity rhythms measured under standard light/dark conditions in rats

Craig LA, Hong NS, Kopp J, McDonald RJ

Brain Res Bull 79(1):53-62, 2009.

It has been theorized that cognitive decline observed in Alzheimer’s disease is in part due to disruption of the circadian rhythm (CR) in these patients. Some basal forebrain cholinergic neurons project to the suprachiasmatic nucleus, which is responsible for maintenance of CR. Rats received two injections totaling 7.5 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum/diagonal band of Broca. Lesioned animals did not show any evidence of CR disruption.

Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms

Goz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP

PLoS ONE 3(9):e3153, 2008.

Retinal ganglion cells expressing melanopsin photopigment are thought to be involved in non-image forming visual responses to light. The authors had a custom conjugate made between saporin and an anti-melanopsin antibody. A 400-ng injection of the melanopsin-SAP (now available as Cat. #IT-44) conjugate into the eye of a mouse resulted in a loss of the targeted cells. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data indicates that melanopsin-containing cells are involved in the response to certain non-image forming visual input.