2001 Targeting Trends Review

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)

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)

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)

Turchi J, Sarter M (2000) Cortical cholinergic inputs mediate processing capacity: Effects of 192 IgG-saporin-induced lesions on olfactory span performance. Eur J Neurosci 12:4505-4514.

Summary: Many experiments support the theory that the basal forebrain (BF) is involved in major aspects of attention that influence learning and memory. Elimination of cholinergic neurons in the BF by 192-Saporin (Cat. #IT-01) has been shown to reduce the ability of rats to perform a task while paying attention to more than one thing. The authors tested the treated rat’s ability to identify one olfactory stimuli from an increasing amount of such stimuli. While the performance of the treated rats returned to control levels within four weeks post-lesion, their performance reflected increased time between tests. These data indicate that cholinergic neurons of the BF play a role in attentional capacities.

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

Villa AEP, Tetko IV, Dutoit P, Vantini G (2000) Non-linear cortico-cortical interactions modulated by cholinergic afferences from the rat basal forebrain. BioSystems 58:219-228. doi: 10.1016/s0303-2647(00)00126-x

Summary: Elimination of the cholinergic neurons of the basal forebrain (BF) is an excellent model for some aspects of Alzheimer’s Disease (AD). 192-Saporin (Cat. #IT-01) is a very effective tool for elimination of cholinergic neurons in the BF. Villa et al. investigate whether field potential changes in the brains of lesioned animals mimic changes observed in the brains of human AD patients. The data presented indicate depletion of cholinergic neurons from the BF of both rats and humans produces similar changes in field potential.

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

Haas CA, Hollerbach E, Deller T, Naumann T, Frotscher M (2000) Up-regulation of growth-associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria-fornix transection. Eur J Neurosci 12:4233-4242. doi: 10.1046/j.0953-816x.2000.01329.x

Summary: Axonal growth and regeneration is limited in adult mammals, however, if injured CNS neurons are in an environment permissive for growth, they can regenerate. Transection of septohippocampal fibers is a widely used method for studying CNS neuron response to injury. These fibers are composed of both cholinergic and GABAergic neurons. Haas et al. used a combination of cholinergic lesioning by 192-Saporin (Cat. #IT-01) and double staining to investigate whether both cell types were involved in neuron regeneration. The findings show that both transmitter phenotypes up-regulate mRNA levels of a protein associated with growth and synaptogenesis in developing neurons, and plasticity in adult neurons.

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

Wiley RG, Kline IV RH (2000) Neuronal lesioning with axonally transported toxins. J Neurosci Methods 103:73-82. doi: 10.1016/S0165-0270(00)00297-1

Summary: Functional neuroanatomy studies have long utilized lesioning. Given the complexity of heterogeneous neuron populations conventional lesioning methods have proved relatively crude, and have provided limited information. Wiley and Kline detail some of the immunotoxins utilizing saporin as well as neuropeptide-saporin conjugates that have found use in recent neurological research. These products include SP-SAP (Cat. #IT-07), which eliminates neurons expressing the neurokinin 1 receptor, 192-Saporin (Cat. #IT-01), which eliminates neurons expressing the p75 receptor in rats, anti-DBH-SAP (Cat #IT-03), which destroys noradrenergic and adrenergic neurons, and OX7-SAP (Cat. #IT-02), which is a suicide transport agent targeting all rat neurons. The authors also discuss some of the protocols and methods utilized with these compounds.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), Anti-DBH-SAP (Cat. #IT-03), SP-SAP (Cat. #IT-07)

McGaughy J, Everitt BJ, Robbins TW, Sarter M (2000) The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251-263. doi: 10.1016/s0166-4328(00)00262-x

Summary: Review and comparison of immunolesioning techniques.

Related Products: 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15)

Schreihofer AM, Stornetta RL, Guyenet PG (2000) Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat. J Physiol 529(1):221-236. doi: 10.1111/j.1469-7793.2000.00221.x

Summary: The rostral ventrolateral medulla (RVLM) controls and maintains basal sympathetic vasomotor tone, and is also vital to many sympathetic reflexes. Sympathetic nerve activity and arterial pressure correlate with the C1 adrenergic neurons in the RVLM, but there are also non-catecholaminergic neurons present. Schreihofer et al. used anti-DBH-SAP (Cat. #IT-03) to eliminate the C1 cells of the RVLM to investigate the non-catecholaminergic neuron contribution to vasomotor tone. Their data indicate C1 cells are necessary for full expression of sympathoexitatory responses generated by the RVLM.

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

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