targeted-toxins

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)

Beninger RJ, Dringenberg HC, Boegman RJ, Jhamandas K (2001) Cognitive effects of neurotoxic lesions of the nucleus basalis magnocellularis in rats: differential roles for corticopetal versus amygdalopetal projections. Neurotox Res 3(1):7-21. doi: 10.1007/BF03033227

Summary: The cholinergic hypothesis states that projections of cholinergic neurons from the nucleus basalis magnocellularis to cortical and amygdalar targets are important in memory. This review discusses the work done on the cholinergic hypothesis using non-specific lesioning agents such as ibotenate and quisqualate, and the specific targeted conjugate 192-Saporin (Cat. #IT-01). The authors conclude that cholinergic targets in both the cortex and amygdala are important for the control of memory.

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

Baxter MG (2001) Effects of selective immunotoxic lesions on learning and memory. (eds. Hall WA). In: Immunotoxin Methods and Protocols. Methods in Molecular Biology. 166:249-265. Humana Press. doi: 10.1385/1-59259-114-0:249

Summary: Dr. Baxter presents a brief review of studies using immunotoxins to study learning and memory. In particular, this chapter focuses on the use of 192-Saporin (Cat. #IT-01) for elimination of basal forebrain cholinergic neurons and cerebellar Purkinje cells.

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

Wiley RG (2001) Toxin-induced death of neurotrophin-sensitive neurons. (eds. Rush RA). In: Neurotrophin Protocols. Methods in Molecular Biology. 169:217-222. Humana Press. doi: 10.1385/1-59259-060-8:217

Summary: Wiley discusses some of the specifics of using 192-Saporin (Cat. #IT-01) to eliminate cells expressing the rat p75 low-affinity nerve growth factor receptor. Wiley also describes the sequence of events following treatment with 192-Saporin from binding of the immunotoxin through ribosomal inactivation and cell death. Methods of handling the immunotoxin and injection are also addressed.

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

Schreihofer A (2001) Featured Article: Immunolesioning: From spinal cord to brain. Targeting Trends 2(1)

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

Read the featured article in Targeting Trends.

See Also:

• Schreihofer AM et al. Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DBH-saporin. Am J Physiol Regul Integr Comp Physiol 279:R729-R742, 2000.
• Schreihofer AM et al. Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats. Am J Physiol Regul Integr Comp Physiol 279:R1753-R1762, 2000.
• Schreihofer AM et al. Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat. J Physiol 529(1):221-236, 2000.

Perry T, Hodges H, Gray JA (2001) Behavioural, histological and immunocytochemical consequences following 192 IgG-Saporin immunolesions of the basal forebrain cholinergic system. Brain Res Bull 54(1):29-48. doi: 10.1016/s0361-9230(00)00413-5

Summary: 192-Saporin (Cat. #IT-01) has been used extensively as a model for Alzheimer’s Disease. The neuronal deficits caused by intraparenchymal forebrain injections (0.3-0.51 µg/µl) are apparent during tasks demanding attentional processing, but not standard tasks of learning and memory. Perry et al. compare the testing strategies for each deficit. They find that the water maze may not demand enough attentional processing to demonstrate deficits caused by this lesion. The authors also study long-term effects of 192-Saporin in rats. Although the authors produced very useful data at five to six months, they found evidence of an inflammatory response and non-specific cell death eleven months post treatment, indicating 192-Saporin may be problematic for very long-term experiments.

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

Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Kobilka BK, Hashimoto T, Maze M (2000) Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of a2B adrenoceptors. J Neurosci 20(24):9242-9251. doi: 10.1523/JNEUROSCI.20-24-09242.2000

Summary: Nitrous oxide has been used extensively in surgical anesthesia for more than 150 years, but the molecular mechanism of action has not yet been defined. Sawamura et al. investigate whether noradrenergic neurons in the brainstem are involved in the analgesic action of nitrous oxide. The authors injected rats with anti-DBH-SAP (Cat. #IT-03) to destroy pontine noradrenergic neurons. The treated rats demonstrated the usual sedative effects of nitrous oxide, but the analgesic effects were reduced or blocked. Coupled with data from null mice for the alpha2B adrenoceptor, the data indicates that alpha2 adrenoceptor subtypes and ligands are involved in the analgesic but not sedative effects of nitrous oxide.

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

Jasmin L, Janni G, Moallem TM, Lappi DA, Ohara PT (2000) Schwann cells are removed from the spinal cord after effecting recovery from paraplegia. J Neurosci 20(24):9215-9223. doi: 10.1523/JNEUROSCI.20-24-09215.2000

Related Products: CTB-SAP (Cat. #IT-14)