targeted-toxins

Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018

Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)

Bostad M, Kausberg M, Weyergang A, Olsen C, Berg K, Høgset A, Selbo P (2014) Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization. Mol Pharm 11:2764-2776. doi: 10.1021/mp500129t

Summary: CD44 is known as a common cancer stem cell (CSC) marker. Given that CSC’s seem to have the ability to resist many therapeutic agents, the authors investigated the use of photochemical internalization (PCI) while targeting CD44-expressing CSC’s. An immunotoxin was constructed by biotinylating a pan CD44 antibody and combining it with Streptavidin-ZAP (Cat. #IT-27) at a 4:1 biotinylated antibody to Streptavidin-ZAP molar ratio. Various cancer cell lines were incubated with the toxin at a concentration of 0.825 nM. The toxin showed specific cytotoxicity to CD44-expressing cell lines, demonstrating the efficacy of PCI in conjunction with targeted toxins to treat some cancers

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD44-SAP (Cat. #IT-72)

Lee CL, Rajkumar R, Dawe GS (2014) Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus. Targeting Trends 15(2)

Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Lee LC et al. Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate. Brain Res 1543:179-190, 2014.

Jeong D, Lee J, Lee S, Chang W, Kim S, Chang J (2014) Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis. Biomed Res Int 2014:568587. doi: 10.1155/2014/568587

Summary: Deep brain stimulation (DBS) is a technique by which electrical impulses are applied to specific areas of the brain as therapy for various disorders. In this work the authors examined the mechanisms by which DBS can treat dementia. Rats received 5.04 μg intracerebroventricular injections of 192-IgG-SAP (Cat. #IT-01); some rats also received an electrode implanted into the medial septum. Lesioned animals displayed deficits in water maze testing – this deficit was eliminated for the group that received electrical stimulation to the medial septum. The stimulated group also displayed an increase in hippocampal cholinergic activity as well as neurogenesis, indicating that DBS has therapeutic potential.

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

Carr F, Géranton S, Hunt S (2014) Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn. Mol Pain 10:39. doi: 10.1186/1744-8069-10-39

Summary: Peripheral joint pathology in conditions such as osteoarthritis does not always correlate to the amount of pain experienced, indicating that chronic pain is present. The role of descending facilitation in this form of chronic pain has not been investigated. The authors examined the role of mu opioid receptor-expressing cells in the rostral vental medulla (RVM) in behavioral hypersensitivity seen in joint pain models. Rats received 1.5 pmol of Dermorphin-SAP (Cat. #IT-12) into the RVM. Lesioned animals displayed prolonged attenuation of hypersensitivity, and altered expression of several genes was detected by qPCR, indicating that descending facilitation in the RVM is involved in joint pain behavior.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Bajo V, Leach N, Cordery P, Nodal F, King A (2014) The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex. Eur J Neurosci 40:2922-2940. doi: 10.1111/ejn.12653 PMID: 24945075

Summary: The ferret has become a more common animal model in auditory neuroscience. Unlike rodent models, however, anatomical data describing the organization of the basal forebrain cholinergic system and its projections to the auditory cortex have not been well characterized. Using a variety of methods the authors mapped the architecture of the ferret basal forebrain. IHC was done with several antibodies including anti-ChAT (Cat. #AB-N34AP; 1:1000) and anti-NGFr (Cat. #AB-N07; 1:500). Animals also received 17 μg of ME20.4-SAP (Cat. #IT-15) in a total of 17 injections into the ectosylvian gyrus. The results indicate that acetylcholine is most likely involved in modulation of auditory processing.

Related Products: Choline Acetyltransferase Rabbit Polyclonal, affinity-purified (Cat. #AB-N34AP), NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07), ME20.4-SAP (Cat. #IT-15)

Rastogi S, Unni S, Sharma S, Laxmi T, Kutty B (2014) Cholinergic immunotoxin 192 IgG-saporin alters subicular theta-gamma activity and impairs spatial learning in rats. Neurobiol Learn Mem 114:117-126. doi: 10.1016/j.nlm.2014.05.008

Summary: The authors investigated the role of the subiculum in spatial informational processing, specifically cholinergic modulation of subicular theta-gamma activity. Rats received 50-ng injections of 192-IgG-SAP (Cat. #IT-01) into the ventral subiculum. Lesioned animals displayed altered theta and gamma activity as well as impaired spatial learning. The hippocampal cholinergic innervations remained intact, indicating that cholinergic modulation of theta-gamma activity in the subiculum plays an important role in spatial information processing.

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

Cordier D, Gerber A, Kluba C, Bauman A, Hutter G, Mindt TL, Mariani L (2014) Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy. Cancer Biother Radiopharm 29(5):221-226. doi: 10.1089/cbr.2013.1588

Summary: The neurokinin-1 receptor (NK1r) has been found to be consistently over-expressed in gliomas, making it a potential target for therapeutic strategies. However, treatments with therapies utilizing substance P (SP), the ligand for the NK1r, have at best yielded uneven results. In this work the authors investigated factors that may predict the response to therapies directed at NK1r gliomas. SSP-SAP (Cat. #IT-11) was used at a concentration of 1 nM in cytotoxicity assays on several different glioma cell lines. Using this and other data it was shown that only the cell line with the most full-length NK1r RNA transcripts displayed high levels of binding, internalization, and cell killing necessary for NK1r to be a therapeutic target using SP.

Related Products: SSP-SAP (Cat. #IT-11)

Nunan R, Sivasathiaseelan H, Khan D, Zaben M, Gray W (2014) Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release. Glia 62:1313-1327. doi: 10.1002/glia.22682

Summary: Postnatal and adult learning and memory require hippocampal neurogenesis. Cognitive dysfunction is frequently accompanied by neuroinflammatory pathogenesis, but the pathways by which the immune system affects neurogenesis are unclear. In this work the authors depleted microglia from primary hippocampal cultures by incubating the cells with 100 μg/ml Mac-1-SAP rat (Cat. #IT-33) for 24 hours. The hippocampal cells were then washed and cultured for further experiments. It was found that neural stem/progenitor cells had reduced survival and proliferation in cultures treated with Mac-1-SAP. These data sketch out the framework of an immune-neuronal pathway important in the regulation of hippocampal neurogenesis.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Cao J, Wu T, Zhang L (2014) [Targeted damage of the cerebrospinal fluid-contacting nucleus contributes to the pain behavior and the expression of 5-HT and c-Fos in spinal dorsal horn of rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 30:218-222.

Summary: Pain threshold, 5-hydroxytryptamine (5-HT) expression, and c-Fos expression were measured in rats after treatment with CTB-SAP (Cat. #IT-14). Use of CTB-SAP reduced the number of neurons in the cerebrospinal fluid (CSF)-contacting nucleus over time until no neurons could be detected by the 10th day post-injection. 5-HT and c-Fos expression in the spinal dorsal horn gradually increased, and was negatively correlated with the pain threshold. The data indicate that neurons in the CSF-contacting nucleus are involved in pain regulation, and that expression of 5-HT and c-Fos is part of this regulatory pathway.

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