A New Immunotoxin for Targeting Dopaminergic Neurons

Targeting results with anti-DAT-SAP shown in the Figure are reprinted by permission of Kluwer Academic/Plenum Publishers.The original was published in Cell Mol Neurobiol 23:839-850,2003.

Product information related to cover article: Anti-DAT-SAP (Cat. #IT-25)

Dr. Rania Siam Joins ATS Team of Scientists

Substance P-Saporin (SP-SAP) Drug Development Update (article)

• Vierck CJ, Kline RH, Wiley RG (2003) Intrathecal substance p-saporin attenuates operant escape from nociceptive thermal stimuli. Neuroscience 119(1):223-232. (SP-SAP, Cat. #IT-07)
• Chiken S, Tokuno H (2003) Ablation of striatal interneurons influences activities of entopeduncular neurons. Neuroreport 14(5):675-678. (SP-SAP, Cat. #IT-07)
• Mistlberger RE, Antle MC, Kilduff TS, Jones M (2003) Food- and light-entrained circadian rhythms in rats with hypocretin-2-saporin ablations of the lateral hypothalamus. Brain Res 980(2):161-168. (Orexin-SAP, Cat. #IT-20)
• Calza L, Giuliani A, Fernandez M, Pirondi S, D'Intino G, Aloe L, Giardino L (2003) Neural stem cells and cholinergic neurons: Regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci U S A 100(12):7325-7330. (192-IgG-SAP, Cat. #IT-01)
• Jasmin L, Boudah A, Ohara PT (2003) Long-term effects of decreased noradrenergic central nervous system innervation on pain behavior and opioid antinociception. J Comp Neurol 460(1):38-55. (Anti-DBH-SAP, Cat. #IT-03)
• Lam TT, Leranth C (2003) Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats. Eur J Neurosci 17(10):1997-2005. (192-IgG-SAP, Cat. #IT-01)

Recent Scientific References

• Lam TT, Leranth C (2003) Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats. Eur J Neurosci 17(10):1997-2005. (192-IgG-SAP, Cat. #IT-01)
• Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C (2003) Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology 144(4):1357-1367. (Anti-DBH-SAP, Cat. #IT-03)
• Rudick CN, Gibbs RB, Woolley CS (2003) A role for the basal forebrain cholinergic system in estrogen-induced disinhibition of hippocampal pyramidal cells. J Neurosci 23(11):4479-4490. (192-IgG-SAP, Cat. #IT-01)
• Feldman JL, Mitchell GS, Nattie EE (2003) Breathing: Rhythmicity, Plasticity, Chemosensitivity. Annu Rev Neurosci 26:239-266. (SP-SAP, Cat. #IT-07 and Anti-SERT-SAP, Cat. #IT-23)
• Bailey AM, Rudisill ML, Hoof EJ, Loving ML (2003) 192 IgG-saporin lesions to the nucleus basalis magnocellularis (nBM) disrupt acquisition of learning set formation. Brain Res 969(1-2):147-159. (192-IgG-SAP, Cat. #IT-01)
• Nakatsuka T, Tsuzuki K, Ling JX, Sonobe H, Gu JG (2003) Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord. J Neurophysiol 89(6):3243-3252. (IB4-SAP, Cat. #IT-10)
• Hilgert M, Hartmann J, Loffelholz K, Jeltsch H, Cassel JC, Klein J (2003) Effects of septal grafts on acetylcholine release from rat hippocampus after 192 IgG-saporin lesion. Neurochem Res 28(3-4):467-472. (192-IgG-SAP, Cat. #IT-01)

Targeting Talk: Dosing, Volume, and Animal Care

• When performing intraparenchymal injections of immunotoxin, what is the proper volume to use? Is it better to induce two half-portions per hemisphere or is a higher concentration better? At what concentration do you expect necrosis or inflammation?
  

Targeting Talk: Dosing, Volume, and Animal Care

• I have been doing research with 192-Saporin for 2-3 years now. I have read in the literature that animals with cholinergic lesions often get sick following surgery and require potatoes, apples, lettuce and saline injections. They may even stop eating or drinking all together. I have followed these practices in the past, but stopped when it didn't seem to make a difference. (I use a very small insignificant dose that is not prone to make animals ill). This is the first death I have had even remotely possibly related to the toxin. In short, the animal lost 64 grams over a period of 2 weeks, and expired 1-2 days thereafter. I weighed her at death and she was 139 grams (91 gram difference from her initial surgery weight). The rats in our colony are fed and given water ad libitum. However, we think that she dehydrated. She was given the same dose (1.1 microliters) as all of the other rats in the experiment. I do have other rats that were given injections from the same lot that do not appear to be sick or losing weight. I'm not sure what you can do with this information, but I would be grateful for whatever help you can offer.
• Another one of my 192-Saporin-treated rats is having an adverse reaction, including paralysis of the lower extremities. She has lost 40 grams in the past 3-4 days. Could this be Purkinje cell damage; does that happen after five weeks?
  

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