targeted-toxins

Bienkowski MS, Rinaman L (2008) Noradrenergic inputs to the paraventricular hypothalamus contribute to hypothalamic-pituitary-adrenal axis and central Fos activation in rats after acute systemic endotoxin exposure. Neuroscience 156(4):1093-1102. doi: 10.1016/j.neuroscience.2008.08.011

Summary: Noradrenergic (NA) neurons in the central nervous system are activated during the immune response to systemic lipopolysaccharide (LPS). The authors tested whether these neurons with axonal inputs to the paraventricular nucleus (PVN) were necessary for LPS-directed Fos expression and increase of plasma corticosterone. Rats received 44-ng bilateral injections of anti-DBH-SAP (Cat. #IT-03) into the medial PVN then were challenged with i.p. LPS. Lesioned animals had attenuated Fos activation and smaller than normal increases in plasma corticosterone.

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

Craig LA, Hong NS, Kopp J, McDonald RJ (2009) Selective lesion of medial septal cholinergic neurons followed by a mini-stroke impairs spatial learning in rats. Exp Brain Res 193(1):29-42. doi: 10.1007/s00221-008-1592-5

Summary: 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.

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

Q: I am planning an experiment to investigate the effects of ablation of spinal NK-1r-expressing cells (using intrathecal injection of SSP-SAP, Cat. #IT-11). In the first part of the experiment I want to destroy the NK-1r-expressing cells before surgical modification. I am unsure how long after injection of SSP-SAP I should carry out the surgery. I was thinking of carrying out surgery at the two-week time point as in a 2007 Neuroscience paper by Wiley et al. Their immunocytochemistry showed a large reduction in staining at this time point. Any advice you could give me would be much appreciated.

A: Two weeks is probably fine. Generally cells begin to lose function at four days, but people wait longer because there is a clean-up by microglia/macrophage that removes the markers that people use for detection/demonstration of efficacy. Mantyh et al. were conservative with a 30-day wait for saporin clearance.

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

References

1. Wiley RG et al. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345, 2007.
2. Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.

Likhtik E (2008) Featured Article: Selective lesions of amygdala intercalated neurons using the Dermorphin-SAP immunotoxin reveal their role in conditioned fear. Targeting Trends 9(4)

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Likhtik E et al. Amygdala intercalated neurons are required for expression of fear extinction. Nature 454(7204):642-645, 2008.

Murillo-Rodriguez E, Liu M, Blanco-Centurion C, Shiromani PJ (2008) Effects of hypocretin (orexin) neuronal loss on sleep and extracellular adenosine levels in the rat basal forebrain. Eur J Neurosci 28(6):1191-1198. doi: 10.1111/j.1460-9568.2008.06424.x

Summary: Adenosine levels in the basal forebrain are thought to regulate the waxing and waning of sleep drive. Rats received bilateral 100-ng injections of orexin-SAP (Cat. #IT-20) into the lateral hypothalamus – resulting in a 94% loss of orexin-containing neurons. Lesioned animals displayed several changes in sleep characteristics, but no increase of adenosine levels after sleep deprivation. The results indicate that sleep changes due to orexin-SAP lesioning occur independently of adenosine levels.

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

Göz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP (2008) Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS ONE 3(9):e3153. doi: 10.1371/journal.pone.0003153 PMID: 18773079

Summary: 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 conjugate into the eye of a mouse resulted in a 57% 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.

Related Products: Melanopsin-SAP (Cat. #IT-44), Melanopsin Rabbit Polyclonal (Cat. #AB-N38), Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39), Rabbit IgG-SAP (Cat. #IT-35)

Mandolesi L, De Bartolo P, Foti F, Gelfo F, Federico F, Leggio MG, Petrosini L (2008) Environmental enrichment provides a cognitive reserve to be spent in the case of brain lesion. J Alzheimers Dis 15:11-28. doi: 10.3233/jad-2008-15102 PMID: 18780964

Summary: The cognitive reserve model suggests individuals can develop resources that reduce the risk of later cognitive impairment. This theory was tested by raising rats in standard vs. enriched environments then lesioning the animals with 192-IgG-SAP (Cat. #IT-01). A total of 0.8 µg of 192-IgG-SAP was administered in bilateral injections, followed by various behavioral tests. It was found that animals raised in an enriched environment had reduced cognitive impairment following forebrain lesions.

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

Colombari DS, Pedrino GR, Freiria-Oliveira AH, Korim WS, Maurino IC, Cravo SL (2008) Lesions of medullary catecholaminergic neurons increase salt intake in rats. Brain Res Bull 76:572-578. doi: 10.1016/j.brainresbull.2008.04.001

Summary: Catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) are thought to contribute to cardiovascular regulation and body fluid homeostasis. Bilateral 6.3-ng injections of anti-DBH-SAP (Cat. #IT-03) were administered to the CVLM of rats. Saporin (Cat. #PR-01) was used as a control. After lesioning and challenge with either furosemide/captopril or water deprivation, intake of 0.3 M NaCl and water were observed. The data indicate medullary catecholaminergic neurons play an inhibitory role in sodium appetite.

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

Liao D, Lin PH, Yao Q, Chen C (2008) Vascular smooth cell proliferation in perfusion culture of porcine carotid arteries. Biochem Biophys Res Commun 372(4):668-673. doi: 10.1016/j.bbrc.2008.05.117

Summary: Basic fibroblast growth factor is highly effective in stimulating smooth muscle cell (SMC) proliferation. The authors used FGF-SAP (Cat. #IT-38) to help characterize a model of vascular SMC proliferation with porcine carotid arteries. Arteries isolated from pigs were cultured under several different conditions, one of which included FGF-SAP at a concentration of 0.4 nM. In all cases the arteries maintained viability for up to 96 hours. SMC proliferation was drastically reduced in the arteries treated with FGF-SAP. [Note, FGF-SAP is not ATS.]

Related Products: FGF-SAP (Cat. #IT-38)

Harle P, Pongratz G, Albrecht J, Tarner IH, Straub RH (2008) An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum 58:2347-2355. doi: 10.1002/art.23628

Summary: The sympathetic nervous system can play conflicting roles in collagen-induced arthritis (CIA). CD4+CD25+ T cells can play an immunoregulatory effect in this system depending on the expression of the FoxP3 transcription factor. Mice received 5 µg intraperitoneal injections of anti-DBH-SAP (Cat. #IT-03) to induce an early sympathectomy. The results indicate that the sympathetic nervous system increases disease severity in CIA by stimulating some of the proinflammatory aspects of CD4+CD25+ T cells.

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