targeted-toxins

Easton A, Phil D, Fitchett A, Eacott MJ, Baxter MG (2010) Cholinergic innervation of the hippocampus is not neccesary for episodic memory, but is required for context-place learning in rats. Neuroscience 2010 Abstracts 99.27/KKK13. Society for Neuroscience, San Diego, CA.

Summary: Loss of cholinergic cortical input is associated with diseases in which episodic memory impairment is a prominent feature, but the degree to which this neurochemical lesion can account for memory impairment in humans with neurodegenerative diseases remains unclear. Removal of cholinergic input to hippocampus impairs some of its functions in memory, perhaps by reducing the plasticity of information representation within the hippocampus, but the role of cholinergic hippocampal input in episodic-like memories has not been investigated. To address this question we tested rats with selective lesions of basal forebrain neurons in the medial septum and vertical limb of the diagonal band (MS/VDB), which contains hippocampal-projecting cholinergic neurons, on a task of integrated memory for objects, places, and contexts (“what-where-which” memory). This task serves as a rodent model of human episodic memory (episodic-like memory) and is sensitive to damage to the hippocampal system. Rats with lesions of cholinergic MS/VDB neurons performed as well on the what-where-which task as controls, but were impaired in a task that simply required them to associate places with contexts (“where-which” memory). Thus, episodic-like memories that rely on the hippocampus do not require cholinergic neuromodulation to be formed. Nevertheless, some more specific aspects of where-which memory, which may be more dependent on the plasticity of hippocampal spatial representations, require acetylcholine. These results suggest that cholinergic projections to hippocampus are not necessary for episodic memory, and furthermore, that hippocampal spatial representations may be to some extent dissociable from episodic memory function.

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

Gompf HS, Mathai C, Fuller PM, Wood DA, Pedersen NP, Saper CB, Lu J (2010) Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551. doi: 10.1523/JNEUROSCI.3037-10.2010

Objective: To examine arousal due to environmental stimuli after lesioning of the Locus ceruleus (LC).

Summary: Lesioned animals did not show sustained neurobehavioral and EEG arousal in response to a novel environment. The data suggest sustained attention requires an interaction between the LC and the anterior cingulate cortex.

Usage: Anti-DBH-SAP (0.25-1 µg) was injected into the lateral ventricle of rats.

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

Koenig J, Lecourtier L, Cosquer B, Pereira PM, Cassel J (2011) Spatial memory alterations by activation of septal 5HT(1A) receptors: no implication of cholinergic septohippocampal neurons. Psychopharmacology (Berl) 214(2):437-454. doi: 10.1007/s00213-010-2049-7

Summary: These experiments examined what effect damaged cholinergic neurons would have on memory deficits induced by the 5-HT1A/5-HT7 receptor agonist 8-OH-DPAT. Rats received 0.4 µg injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, delivered through an infusion device. Through use of a water maze test, the authors show that several neuronal populations are involved in processing hippocampal information, and non-cholinergic neurons in this region may be more important than the cholinergic ones for memory processing.

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

Q: In a previous question, you mentioned mixing anti-DBH-SAP (Cat. #IT-03) with a tracer to monitor drug delivery. Which tracer would you recommend? We were thinking of using FluoroGold. If we do not use a tracer, we were thinking of using a neutral red solution to dilute the stock of anti-DBH-SAP in order to be able to visibly see the toxin being injected into the spinal cord. Could there be an issue of pH if we used neutral red with anti-DBH-SAP? Our concern is that the toxin is not being ejected from the pipette tip or that it is not being taken up into the pipette tip as we can not see it (it’s the same color as the mineral oil). We are confident in the targeting of the spinal area for injection as we have previously used FluoroGold only and then were able to visualize it in the area of interest.

A: Our Scientific Advisor, Dr. Ronald G. Wiley, uses Fast Green dye (0.01-0.1% w/v) in the toxin injection solutions. He originally chose Fast Green because intracellular electrophysiologists had long used it while doing intracellular recordings and shown it was non-toxic. Fast Green has more contrast than Neutral Red (easier to see) and does not affect pH significantly. He has used it with many saporin-containing toxins with success.

Dr. Wiley says, “There are two issues when you talk about using “tracers” with targeted toxins: 1) tracing the acute injection volume to be sure it goes into the animal correctly, and 2) tracing the neurons that projected to the injection site and were therefore susceptible to being killed by the toxin.

Dr. Wiley does not use separate anatomic tracers for the immunotoxins, the only agents taken up and retrogradely transported efficiently. Since ATS immunotoxins are so efficient you have to use a high efficiency tracer such as cholera toxin B (but not WGA since it may not play well with saporin).

Dr. Wiley does not favor FluoroGold (a tin compound) because he has seen some local toxicity at FluoroG injection sites which might impair uptake and/or transport of a targeted toxin, and it is not clear if it is compatible with saporin-containing toxins.

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

Lujan HL, DiCarlo SE (2010) Featured Article: Targeted ablation of sympathetic neurons reduces ventricular arrhythmias and autonomic dysreflexia. Targeting Trends 11(4)

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

Read the featured article in Targeting Trends.

See Also:

• Lujan HL et al. Targeted Ablation of Cardiac Sympathetic Neurons Reduces the Susceptibility to Ischemia-Induced Sustained Ventricular Tachycardia in Conscious Rats. Am J Physiol Heart Circ Physiol 298:H1330-H1339, 2010.
• Lujan HL et al. Targeted Ablation of Mesenteric Projecting Sympathetic Neurons Reduces the Hemodynamic Response to Pain in Conscious Spinal Cord Transected Rats. Am J Physiol Regul Integr Comp Physiol 298(5):R1358-1365, 2010.

Do MTH, Yau K (2010) Intrinsically photosensitive retinal ganglion cells. Physiol Rev 90(4):1547-1581. doi: 10.1152/physrev.00013.2010

Summary: This review presents recent data that has established the importance of intrinsically photosensitive retinal ganglion cells (ipRPG) in nonimage visual functions. The use of melanopsin-SAP (Cat. #IT-44) in both mice and rats is discussed. It is of note that depletion of ipRPG’s using melanopsin-SAP resulted in deficits in communication to nonimage regions of the brain, but image vision appeared normal.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Lyons AM, Thiele TE (2010) Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31(12):2193-2199. doi: 10.1016/j.peptides.2010.09.009

Summary: Neuropeptide Y (NPY) in the hypothalamus is known to modulate feeding behavior. In this work the authors used bilateral 48 ng injections of NPY-SAP (Cat. #IT-28) into the central amygdala or basomedial hypothalamus (BMH) of rats to investigate the role of NPY in anxiety. Blank-SAP (Cat. #IT-21) was used as a control. Injections into the amygdala increased anxiety-like behavior, while injections into the BMH reduced anxiety-like behavior. BMH injections also initiated an increase of NPY-1 receptor expression in the basolateral nuclei of the amygdala.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Di Sebastiano AR, Wilson-Perez HE, Lehman MN, Coolen LM (2011) Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats. Horm Behav 59(1):1-8. doi: 10.1016/j.yhbeh.2010.09.006

Summary: The neuropeptide orexin is important in the feedback mechanisms of food intake and drugs of abuse. This work investigates the role of orexin in sexual reward in male rats. Two 200 ng bilateral hypothalamic injections of orexin-SAP (Cat. #IT-20) were made into each hemisphere. Blank-SAP (Cat. #IT-21) was used as a control. Although it was shown orexin neurons are activated by sexual reward cures, the data suggest that orexin is not essential for sexual performance and motivation.

Related Products: Orexin-B-SAP (Cat. #IT-20), Blank-SAP (Cat. #IT-21)

Wang Y, Mu X, Liu Y, Zhang X, Wu A, Yue Y (2011) NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might improve intractable visceral pain of cancer origin. Med Hypotheses 76(1):102-104. doi: 10.1016/j.mehy.2010.08.042

Summary: There is evidence that spinal post-synaptic dorsal column neurons begin to express neurokinin-1 receptors after visceral stimulation. The authors discuss using this expression profile to target SSP-SAP (Cat. #IT-11) to these neurons and eliminate them. This use of ‘molecular neurosurgery’ may be a replacement for traditional neurosurgery for the treatment of cancer-related visceral pain.

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

Baskin DG, Kim F, Gelling RW, Russell BJ, Schwartz MW, Morton GJ, Simhan HN, Moralejo DH, Blevins JE (2010) A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology 151(9):4207-4213. doi: 10.1210/en.2010-0295

Summary: There is evidence to suggest that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain can inhibit food intake by augmenting the cholecystokinin satiety response. In order to add support to this hypothesis the authors used oxytocin-SAP (Cat. #IT-46) to eliminate oxytocin receptive cells in the NTS. Blank-SAP (Cat. #IT-21) was used as a control. 0.5 µl-injections of oxytocin-SAP into the NTS caused reduced satiation effect of CCK-8 and blocked the stimulation of food intake by an oxytocin receptor antagonist.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)