2009 Targeting Trends Review

Nag N, Baxter MG, Berger-Sweeney JE (2009) Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice. Neurosci Lett 452:247-251. doi: 10.1016/j.neulet.2009.01.006

Summary: The authors tested a new version of mu p75-SAP (Cat. #IT-16) in mice. Mice received bilateral injections of 0.65 or 1.3 µg of immunotoxin into each lateral ventricle. Both amounts produced a complete loss of cholinergic neurons in the medial septum, while a dose-dependent loss of cholinergic neurons was seen in the nucleus basalis magnocellularis.

Related Products: mu p75-SAP (Cat. #IT-16)

Montero M, Gonzalez B, Zimmer J (2009) Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152. doi: 10.1016/j.brainres.2009.06.097

Summary: Data has shown microglia to be both neuroprotective and neurodegenerative in cerebral ischemia. This study presents a method for removing microglia from hippocampal slice cultures. Hippocampal slices from mouse were incubated with 13 nM Mac-1-SAP (Cat. #IT-06) for 3 to 7 days. The slices were then exposed to oxygen-glucose deprivation. Those cultures lacking microglia displayed significantly higher degeneration of CA1 pyramidal cells, indicating a neuroprotective role for microglia in this model.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

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Lawhorn C, Smith DM, Brown LL (2009) Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task. Neuroscience 163(1):109-119. doi: 10.1016/j.neuroscience.2009.05.021

Summary: The functional role of basal ganglia striosomes is not well understood. In order to examine these cells in the context of motor behavior the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into several areas of the striatum of mice (saporin, Cat. #PR-01, was used as a control). The animals were then evaluated in complex motor tasks involving the use of striatal circuitry. Animals receiving dermorphin-SAP showed deficits in specific motor tasks corresponding to the extent of the lesion.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)

Penaloza-MacMaster P, Masopust D, Ahmed R (2009) T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction. Immunology 128:164-171. doi: 10.1111/j.1365-2567.2009.03080.x

Summary: Although antigen-specific T cells are vital to adaptive immune responses, they also contribute to a variety of diseases. In this work the authors examined the possibility of selectively removing epitope-specific T cells while preserving immune function. Biotinylated MHC class I tetramers were combined with streptavidin-ZAP (Cat. #IT-27) and used in a mouse transferable T-cell-dependent neurological disease model. This technique resulted in a dramatic reduction in targeted antigen specific T cells with no observable bystander toxicity.

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

Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, Sejnowski TJ, Tuszynski MH (2009) NGF is essential for hippocampal plasticity and learning. J Neurosci 29:10883-10889. doi: 10.1523/JNEUROSCI.2594-09.2009

Summary: This work aimed to define NGF modulation of plasticity and function in adults. Rats received 50 ng injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals exhibited impaired retention of spatial memory and significantly reduced hippocampal long term potentiation. These results indicate that NGF modulates neuronal plasticity and behavior by exerting effects on cholinergic projections to hippocampal and cortical targets.

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

Zhu J, Xu W, Wang J, Ali SF, Angulo JA (2009) The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice. J Neurochem 111(3):656-668. doi: 10.1111/j.1471-4159.2009.06330.x

Summary: This study examined the role of neurokinin-1 receptors (NK1R) on the methamphetamine-induced apoptosis of striatal neurons. 4 ng of SSP-SAP (Cat. #IT-11) or the control, saporin (Cat. #PR-01), was administered to the striatum of mice. Ablation of NK1R-expressing striatal neurons resulted in a significant reduction of methamphetamine-induced apoptosis. The data suggests that the NK1R circuitry in the striatum may be a target for treatment of methamphetamine abuse.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)

Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF (2009) Cellular basis of itch sensation. Science 325:1531-1534. doi: 10.1126/science.1174868

Summary: Whether itch and pain use separate neuronal pathways has long been a subject of debate. The authors injected 400 ng of bombesin-SAP (Cat. #IT-40) into the intrathecal space of mice and examined itch and pain behavior. Lesioned mice had dramatic deficits in all itch behavior tested regardless of the histamine dependence of the itch. All pain behaviors, however, were left intact. These data indicate that the gastrin-releasing peptide receptor-expressing neurons are essential for itch transmission.

Related Products: Bombesin-SAP (Cat. #IT-40)

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Ma J, Tai SK, Leung LS (2009) Ketamine-induced deficit of auditory gating in the hippocampus of rats is alleviated by medial septal inactivation and antipsychotic drugs. Psychopharmacology (Berl) 206:457-467. doi: 10.1007/s00213-009-1623-3

Summary: Schizophrenic patients do not experience the usual diminished response to repeated stimuli, otherwise known as gating. Gating loss can be caused by the administration of some psychotomimetic drugs. This study used 170 ng injections of 192-IgG-SAP (Cat. #IT-01) to examine the effect of ketamine on sensory gating loss. Elimination of septohippocampal cholinergic neurons alleviated the disruption of auditory gating caused by ketamine.

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

Fargo KN, Foster AM, Sengelaub DR (2009) Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons. Dev Neurobiol 69:825-835. doi: 10.1002/dneu.20743

Summary: Previous work has demonstrated that testosterone treatment can prevent dendritic atrophy due to death of nearby motoneurons. This experiment examined whether this protection extends to motor activation. Rats received a 1 µg injection of CTB-SAP (Cat. #IT-14) into each of the right bulbocavernosus and levator ani muscles. Animals treated with testosterone preserved more of the activity duration than untreated animals, as well as no decrease in motoneuron recruitment.

Related Products: CTB-SAP (Cat. #IT-14)

Zhang L, Moffatt-Bruce SD, Gaughan AA, Wang JJ, Rajab A, Hadley GA (2009) An anti-CD103 immunotoxin promotes long-term survival of pancreatic islet allografts. Am J Transplant 9:2012-2023. doi: 10.1111/j.1600-6143.2009.02735.x PMID: 19645708

Objective: To determine whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in organ allograft rejection and graft-vs-host disease.

Summary: These data document that depletion of CD103 expressing cells represents a viable strategy for therapeutic intervention in allograft rejection.

Usage: Recipient C57BL/6 mice received 2.0 mg/kg M290-SAP or Rat IgG-SAP on day 3 post-transplantation.

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)