2001 Targeting Trends Review

Lamprea MR, Cardenas FP, Silveira R, Morato S, Walsh TJ (2000) Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: Forebrain cholinergic mechanisms. Behav Brain Res 117:97-105. doi: 10.1016/s0166-4328(00)00294-1

Summary: The septo-hippocampal pathway has been implicated in many behavioral processes such as learning, anxiety, and motivation. Using 192-Saporin (Cat. #IT-01) to lesion the cholinergic neurons of the medial septum of rats, the authors demonstrate changes in exploratory behavior associated with learning, but no changes in anxiety-associated behavior in their elevated plus maze paradigm.

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

Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ (2001) Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 21(18):7273-7283. doi: 10.1523/JNEUROSCI.21-18-07273.2001 PMID: 11549737

Summary: Orexin (also knows as hypocretin) peptides are produced exclusively by neurons in the lateral hypothalamus, however non-specific lesioning in this region has not produced narcoleptic-like sleep. Gerashchenko et al. use orexin-SAP (490 ng/0.5 µl; Cat. #IT-20) to specifically eliminate orexin neurons in rats. The treated rats displayed several sleep disturbances found in narcolepsy, including increased slow-wave sleep, and sleep-onset REM sleep periods. The data suggest that orexin-SAP can be used to create a model for narcolepsy in rats.

Related Products: Orexin-B-SAP (Cat. #IT-20), Saporin Goat Polyclonal, affinity-purified FITC-labeled (Cat. #AB-15APFL), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP)

Gerashchenko D, Salin-Pascual R, Shiromani PJ (2001) Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta. Brain Res 913:106-115. doi: 10.1016/s0006-8993(01)02792-5

Summary: Hypocretin, also known as orexin, neurons are located only in the lateral hypothalamus. Recently, the loss of these neurons was shown to be associated with narcolepsy. The authors used orexin-SAP (100 ng/0.5 µl; Cat. #IT-20) to eliminate parvalbumin and cholinergic neurons (orexin B receptor-expressing) in the rat medial septum. They used 192-Saporin (1 µg/ 1 µl; Cat. #IT-01) to contrast the effect and eliminate only cholinergic neurons (NGF/p75 receptor-expressing). Hippocampal theta activity was completely eliminated in orexin-SAP treated rats by day 12, suggesting that orexin neurons influence cognitive processes critical for survival.

Related Products: 192-IgG-SAP (Cat. #IT-01), Orexin-B-SAP (Cat. #IT-20)

Harrell LE, Parsons D, Kolasa K (2001) Hippocampal sympathetic ingrowth occurs following 192-IgG-saporin administration. Brain Res 911:158-162. doi: 10.1016/s0006-8993(01)02626-9

Summary: Electrolytic lesions of the medial septal region in rats cause peripheral sympathetic fibers from the superior cervical ganglia to grow into the cholinergically-denervated areas of the hippocampus. This lesioning method is non-specific and disrupts several other cell types in the area of the lesion. The authors infused 192-Saporin (1 µg/10 µl saline into medial septum; Cat. #IT-01) to eliminate only the cholinergic neurons, leaving other cell types intact. Hippocampal sympathetic ingrowth still occurs when only the cholinergic neurons are eliminated, indicating that this occurrence is in response to the loss of cholinergic projections from the medial septum.

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

Daniels D, Miselis RR, Flanagan-Cato LM (2001) Transneuronal tracing from sympathectomized lumbar epaxial muscle in female rats. J Neurobiol 48(4):278-290. doi: 10.1002/neu.1057

Summary: The authors use pseudorabies virus (PRV) to study central neural networks such as the one controlling the lordosis reflex (increased curvature of the spine). To aid in the separation of the sympathetic nervous system and higher order systems, rats were treated with lumbar injections of anti-DBH-SAP (156 ng to 5 µg; Cat. #IT-03), then labeled with PRV. PRV labeling in the brain was absent in areas associated with vasomotor tone, but persisted in areas implicated in control of the lordosis response.

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

Linster C, Garcia PA, Hasselmo ME, Baxter MG (2001) Selective loss of cholinergic neurons projecting to the olfactory system increases perceptual generalization between similar, but not dissimilar, odorants. Behav Neurosci 115(4):826-833. doi: 10.1037//0735-7044.115.4.826

Summary: Selective cholinergic lesioning of the basal forebrain has been linked to attentional and cognitive deficits. 192-Saporin (Cat. #IT-01) was administered to the horizontal limb of the diagonal band of Broca (0.3 µl at 0.175 µg/µl in each hemisphere) destroying projections to the olfactory bulb and cortex. The results demonstrate cholinergic lesions affect the perceptual qualities of odors, and may possibly represent a general mechanism for cholinergic effects on information processing.

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

Motooka Y, Kondoh T, Nomura T, Tamaki N, Tozaki H, Kanno T, Nishizaki T (2001) Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus. Devel Brain Res 129:119-123. doi: 10.1016/s0165-3806(01)00179-1

Summary: The authors studied the possible role of cholinergic systems in long-term potentiation (LTP), which is one of the most intensively studied models of learning and memory. 192-Saporin (4.2 µg/5 µl, Cat. #IT-01) injections were made in both infant and adult rats and the probability of LTP development was studied in hippocampal slices from animals treated 2 weeks or 2 months before. Cholinergic denervation by 192-Saporin did not affect LTP expression in the infant brain, however, the results strongly suggest that cholinergic systems in the adult brain participate in an LTP pathway.

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

Browne SE, Lin L, Mattsson A, Georgievska B, Isacson O (2001) Selective antibody-induced cholinergic cell and synapse loss produce sustained hippocampal and cortical hypometabolism with correlated cognitive deficits. Exp Neurol 170:36-47. doi: 10.1006/exnr.2001.7700

Summary: The authors used 192-Saporin (two 2.5-µg bilateral injections of 1 µg/µl; Cat. #IT-01) to eliminate cholinergic neurons in the rat, then measured cerebral rates of glucose utilization. The findings show sustained reduction in glucose utilization in the brain regions showing loss of cholinergic neurons, specifically the frontal cortical and hippocampal regions. These same animals demonstrated impaired performance in a Morris water maze. The results reinforce the theory that cholinergic systems influence metabolism and cognition in the cortex and hippocampus.

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

Martin JL, Sloviter RS (2001) Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of substance P. J Comp Neurol 436:127-152. doi: 10.1002/cne.1065

Usage: The authors used SSP-SAP (0.4 ng/10 nl; Cat. #IT-11).

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

Read the featured article in Targeting Trends.

Ferreira G, Meurisse M, Tillet Y, Lévy F (2001) Distribution and co-localization of choline acetyltransferase and p75 neurotrophin receptors in the sheep basal forebrain: implications for the use of a specific cholinergic immunotoxin. Neuroscience 104(2):419-439. doi: 10.1016/s0306-4522(01)00075-6 PMID: 11377845

Summary: ME20.4 is a monoclonal antibody (Cat. #AB-N07) that has been shown to bind the p75 receptor in rabbit, sheep, dog, cat, raccoon, pig, and several primate species. Ferreira et al. investigate ME20.4-SAP (bilateral, 150 µl per ventricle, 50-150 µg total; Cat. #IT-15) use in sheep to assess distribution and localization of p75. The authors demonstrate 80-95% loss of basal forebrain cholinergic neurons and acetylcholinesterase-positive fibers in the hippocampus, olfactory bulb, and entorhinal cortex.

Related Products: ME20.4-SAP (Cat. #IT-15), NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

Hartlage-Rübsamen M, Schliebs R (2001) Sequential upregulation of cell adhesion molecules in degenerating rat basal forebrain cholinergic neurons and in phagocytotic microglial cells. Brain Res 897(1-2):20-26. doi: 10.1016/s0006-8993(01)02093-5

Summary: Neurodegeneration, found in brain disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, is marked by a significant microglial response. This microglial activation is characterized by increased migratory activity and potential cytotoxic action on injured neurons. The interaction of microglial cells with degenerating axons and neural somata is known to be mediated by expression of cell adhesion molecules. The authors use a single intracerebroventricular injection of 192-Saporin (4 µg; Cat. #IT-01) to initiate neurodegeneration of choline acetyltransferase-immunoreactive neurons and follow the expression of two cell adhesion molecules, ICAM-1 and LFA-1, using immunohisto-chemistry. The results indicate that these adhesion molecules may function as intercellular recognition signals through which degenerating cholinergic neurons actively participate in their own targeting and removal by microglia.

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

de Rosa E, Hasselmo ME, Baxter MG (2001) Contribution of the cholinergic basal forebrain to proactive interference from stored odor memories during associative learning in rats. Behav Neurosci 115(2):314-327.

Summary: Proactive interference (PI) is the damaging effect of previously learned information on the acquisition of new, related information. Human patients with basal forebrain (BF) damage due to aneurysms are sensitive to PI. The authors administered 192-Saporin (Cat. #IT-01) to the horizontal limb of the diagonal band of Broca (two 0.2-µl injections of 0.175 µg/µl in each hemisphere) in rats and evaluated performance in an olfactory discrimination task. The treated rats had more difficulty acquiring an overlapping odor pair when muscarinic receptors were blocked by scopalomine. These results indicate that cholinergic neurons have a role in the modulation of PI in associative learning.

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

Zheng F, Khanna S (2001) Selective destruction of medial septal cholinergic neurons attenuates pyramidal cell suppression, but not excitation in dorsal hippocampus field CA1 induced by subcutaneous injection of formalin. Neuroscience 103(4):985-998. doi: 10.1016/s0306-4522(01)00006-9

Summary: Previously, the authors have shown that an injection of formalin in the hindpaw of rats will excite a select population of CA1 pyramidal cells within a larger suppressed population. This response is accompanied by increased theta activation. The authors selectively eliminated medial septal cholinergic neurons using 192-Saporin (0.4 µl; Cat. #IT-01) to investigate the role of these neurons in response to a persistent noxious stimulus such as a formalin injection. The data indicate a CA1 network modulated by cholinergic neurons in the medial septal region may influence pyramidal cell theta and pyramidal cell suppression.

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

Deuchars J, Deuchars S (2001) It’s enough to raise your blood pressure!. Trends Neurosci 24(4):200. doi: 10.1016/s0166-2236(00)01800-2

Summary: The authors review studies completed by Schreihofer and Guyenet using anti-DBH-SAP (Cat. #IT-03) to eliminate C1 adrenergic neurons. The results show that, although C1 neurons play a role in some sympathoexcitatory responses, they are probably not responsible for maintaining sympathetic tone.

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

Sarter M, Bruno JP, Miner LA, McGaughy J (2000) Development of a method for intraparenchymal infusions of 192 IgG-Saporin: a comment on Pizzo et al. (1999) [letter; comment]. J Neurosci Methods 96:169-170. doi: 10.1016/s0165-0270(99)00196-x

Summary: Letter pertaining to use of 192-SAP

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

Ritter S, Bugarith K, Dinh TT (2001) Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation. J Comp Neurol 432(2):197-216. doi: 10.1002/cne.1097

Summary: Control of regulatory responses to low glucose levels in the brain have been linked to catecholaminergic neurons. Studies of these neurons have been hindered by the lack of a selective and precise lesioning agent. Ritter et al. use anti-DBH-SAP (Cat. #IT-03) to create very precise lesions of catecholamine neurons in the paraventricular nucleus of the hypothalamus and spinal cord. Injection of anti-DBH-SAP into the spinal cord eliminates cells with caudal projections while injection into the paraventricular nucleus of the hypothalamus eliminated cells with rostral projections. This ability to selectively eliminate very specific subpopulations of cells is a valuable characteristic in dissecting neuronal function.

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

Ferencz I, Leanza G, Nonobashvili A, Kokaia Z, Kokaia M, Lindvall O (2001) Septal cholinergic neurons suppress seizure development in hippocampal kindling in rats: comparison with noradrenergic neurons. Neuroscience 102(4):819-832. doi: 10.1016/s0306-4522(00)00499-1

Summary: Kindling can be caused in rats by lesioning forebrain cholinergic or noradrenergic projections. Ferencz et al. utilize 192-Saporin (2.5 µg; Cat. #IT-01) to lesion forebrain cholinergic neurons and 6-hydroxydopamine to lesion noradrenergic neurons, administering both compounds by intraventricular injection. Upon comparing various aspects of hippocampal kindling, the authors determine that while both noradrenergic and cholinergic projections to the forebrain exert inhibitory effects, the cholinergic effect is less pronounced and occurs prior to seizure generalization.

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

Paqueron X, Li X, Eisenach JC (2001) p75-expressing elements are necessary for anti-allodynic effects of spinal clonidine and neostigmine. Neuroscience 102(3):681-686. doi: 10.1016/s0306-4522(00)00528-5

Summary: It has been suggested that alpha2-adrenergic agonists produce analgesia by activating spinal cholinergic neurons. The authors reason that since spinal cholinergic neurons in the ventral horn express p75 following peripheral nerve trauma, cholinergic dorsal horn neurons might also. Instead, they find that dorsal horn neurons express little or no p75 under normal conditions or following spinal nerve ligation. Since dorsal horn neurons do not express p75 they are not eliminated by 192-Saporin (0.1-0.6 µg; Cat. #IT-01), but the data indicate that p75-expressing elements do play a role in pain transmission in the dorsal horn. The authors note that when afferents that express p75 are eliminated, mechanical hypersensitivity is unaffected, but the reduction of hypersensitivity by alpha2-adrenergic agonists or cholinergic agents is blocked.

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

Hunt SP, Mantyh PW (2001) The molecular dynamics of pain control. Nature Rev Neurosci 2:83-91. doi: 10.1038/35053509

Summary: Over the last twenty years a great deal of progress has been made in the understanding of how pain is processed and transmitted by the CNS. The authors of this review highlight advances in systems neurobiology, behavioral analysis, genetics, and cell and molecular techniques. One method discussed is the use of the targeted toxin substance P-saporin (SP-SAP, Cat. #IT-07, also available with a more stable analog of substance P, SSP-SAP, Cat. #IT-11). This targeted toxin selectively lesions neurons expressing the NK1 receptor. Injection of SP-SAP into the spinal cord of rats dramatically attenuates the response to chronic pain stimuli, yet leaves acute pain response intact.

Related Products: SP-SAP (Cat. #IT-07), SSP-SAP (Cat. #IT-11)

Hartlage-Rübsamen M, Schliebs R (2001) Rat basal forebrain cholinergic lesion affects neuronal nitric oxide synthase activity in hippocampal and neocortical target regions. Brain Res 889(1-2):155-164. doi: 10.1016/s0006-8993(00)03128-0

Summary: Nitric oxide (NO) mediates a variety of mechanisms in the brain including cortical perfusion, learning and memory, and neuronal plasticity. Cholinergic dysfunction has been associated with some of these same processes, notably reduced cortical cerebral blood flow and impaired performance in learning and memory tasks. The authors use a single intracerebroventricular injection of 192-Saporin (2.8 µg; Cat. #IT-01) to deplete the cholinergic neurons of the basal forebrain. Although total cortical neuronal NO synthase levels are not affected, the activity levels in select neocortical hippocampal neurons are reduced. The data suggest the ratio of catalytically active and inactive cortical NO synthase may be driven in part by basal cholinergic forebrain input.

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