2001 Targeting Trends Review

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.

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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 PMID: 10720682

Summary: Letter pertaining to use of 192-SAP

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

See Also:

• Pizzo DP et al. Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei. J Neurosci Methods 91:9-19, 1999.

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.

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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.

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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)