Targeting Topics 01q2

Up-regulation of growth-associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria-fornix transection.

Haas CA, Hollerbach E, Deller T, Naumann T, Frotscher M.

Eur J Neurosci 12(12):4233-4242, 2000. PMID: 11122335

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.

Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB.

Grindstaff RJ, Grindstaff RR, Cunningham JT.

Am J Physiol Regul Integr Comp Physiol 279(5):R1934-43, 2000. PMID: 11049879

Baroreceptors are one component of the system that buffers acute changes in blood pressure. Part of this control stems from the baroreceptor ability to regulate vasopressin release from the neurohypophysis. Using 192-Saporin (Cat. # IT-01) to specifically eliminate cholinergic neurons in the diagonal band of Broca, Grindstaff et al. demonstrated that these neurons are not utilized in the pathway that relays baroreceptor information to the brain.

Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: forebrain cholinergic mechanisms.

Lamprea MR, Cardenas FP, Silveira R, Morato S, Walsh TJ.

Behav Brain Res 117(1-2):97-105, 2000. PMID: 11099762

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.

Early migratory rat neural crest cells express functional gap junctions: evidence that neural crest cell survival requires gap junction function.

Bannerman P, Nichols W, Puhalla S, Oliver T, Berman M, Pleasure D.

J Neurosci Res 61(6):605-615, 2000. PMID: 10972957

Gap junctions are vital for intercellular communication, especially during development. Neural crest cells develop into several types of neural cells, often migrating as a mass of cells to their final destinations. Bannerman et al. use the anti-p75 antibody (Cat. #AB-N01) to confirm the presence of p75 in neural crest cells. The authors examine how crucial survival signals are communicated during migration and demonstrate that interfering with gap junction formation causes death of neural crest cells.

The molecular dynamics of pain control.

Hunt SP, Mantyh PW.

Nat Rev Neurosci 2(2):83-91, 2001. PMID: 11252998

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.

Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat.

Schreihofer AM, Stornetta RL, Guyenet PG.

J Physiol 529 Pt 1:221-236, 2000. PMID: 11080264

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 sympathoexcitatory responses generated by the RVLM.

Neuronal lesioning with axonally transported toxins.

Wiley RG, Kline IVRH.

J Neurosci Methods 103(1):73-82, 2000. PMID: 11074097

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.

Non-linear cortico-cortical interactions modulated by cholinergic afferences from the rat basal forebrain.

Villa AE, Tetko IV, Dutoit P, Vantini G.

Biosystems 58(1-3):219-228, 2000. PMID: 11164650

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.

Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adrenoceptors.

Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Kobilka BK, Hashimoto T, Maze M.

J Neurosci 20(24):9242-9251, 2000. PMID: 11125002

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 α2B adrenoceptor, the data indicates that α2 adrenoceptor subtypes and ligands are involved in the analgesic but not sedative effects of nitrous oxide.

Cortical cholinergic inputs mediate processing capacity: effects of 192 IgG-saporin-induced lesions on olfactory span performance.

Turchi J, Sarter M.

Eur J Neurosci 12(12):4505-4514, 2000. PMID: 11122361

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 number 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.