targeted-toxins

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)

Vetrivelan R, Saper C, Fuller P (2014) Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions. Nat Sci Sleep 6:57-63. doi: 10.2147/NSS.S53132

Summary: Excessive daytime sleepiness is often treated with modafinil. Armodafinil, the R-isomer of modafinil, has been introduced for clinical use, but little is known about the cellular pathway targeted by these drugs. The authors examined whether armodafinil inhibits the ventrolateral preoptic nucleus (VLPO). Rats received 200-ng injections of orexin-SAP into the VLPO, followed by administration of armodafinil. Lesioned animals displayed increased wakefulness similar to control animals, indicating that armodafinil and modafinil do not act along the VLPO neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Flak J, Myers B, Solomon M, McKlveen J, Krause E, Herman J (2014) Role of paraventricular nucleus-projecting norepinephrine/epinephrine neurons in acute and chronic stress. Eur J Neurosci 39:1903-1911. doi: 10.1111/ejn.12587

Summary: Chronic stress can cause dysregulation of the paraventricular nucleus (PVN) of the hypothalamus, resulting in structural and function changes in the neurons involved. There are data indicating that post-stress enhancement of norepinephrine is involved in the processing of chronic stress. In this work the authors investigated the hypothesis that PVN-projecting norepinephrine/epinephrine (NE/E) neurons are necessary for chronic stress-induced drive of the hypothalamic-pituitary-adrenocortical (HPA) axis. Rats received bilateral 8.82 ng injections of anti-DBH-SAP (Cat. #IT-03) into the PVN. Saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed attenuated peak ACTH, indicating that NE/E neurons are required for ACTH release in the HPA axis during chronic stress.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

Wheeler D, Wan S, Miller A, Angeli N, Adileh B, Hu W, Holland P (2014) Role of lateral hypothalamus in two aspects of attention in associative learning. Eur J Neurosci 40:2359-2377. doi: 10.1111/ejn.12592

Summary: The lateral hypothalamic (LH) region contains both orexin and melanin-concentrating hormone (MCH) neurons. These neurons are unique to the LH but project throughout the brain. In this work the authors examined the role of the LH in specific attentional aspects of associative learning. Rats received unilateral 500 ng injections of orexin-SAP (IT-20) into the LH and were tested in several learning tasks. The lesioned animals displayed impaired behavior that was correlated to the loss of orexin but not MCH neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Shin E, Rogers J, Devoto P, Björklund A, Carta M (2014) Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease. Exp Neurol 257:25-38. doi: 10.1016/j.expneurol.2014.04.011

Summary: Although Parkinson’s disease is usually associated with loss of dopaminergic neurons in the substantia nigra, post-mortem studies have shown that noradrenergic neurons in the locus coeruleus also degenerate. In this work the authors develop a new Parkinson’s disease model by double lesioning with both 6-OHDA into the striatum and 2.5 μg bilateral injections of anti-DBH-SAP (Cat. #IT-03) into the lateral ventricles of rats. Double-lesioned animals performed worse on tests evaluating Parkinson’s disease symptoms than those lesioned only with 6-OHDA. The data suggest that Parkinson’s disease symptoms reflect the loss of both dopaminergic and noradrenergic neurons in the midbrain.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Jokiaho A, Donovan C, Watts A (2014) The rate of fall of blood glucose determines the necessity of forebrain-projecting catecholaminergic neurons for male rat sympathoadrenal responses. Diabetes 63:2854-2865. doi: 10.2337/db13-1753

Summary: Different sets of glucosensors detect insulin-induced hypoglycemia depending on the onset rate. This detection controls the activation of sympathoadrenal counterregulatory responses (CRRs). Slow onset hypoglycemia, common with insulin therapy, is detected by glucosensors in the portal-mesenteric veins. Fast onset is detected by brain elements. The authors lesioned hindbrain catecholaminergic neurons to determine which set of responses-they interact with. Rats received 42 ng bilateral injections of Anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data indicate that these neurons are critical for detection of slow-onset insulin-induced hypoglycemia.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)