targeted-toxins

Power AE, Thal LJ, McGaugh JL (2002) Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala. Proc Natl Acad Sci U S A 99(4):2315-2319. doi: 10.1073/pnas.022627799

Summary: There is evidence that memory consolidation (retention) can be modulated by drugs and stress hormones acting in the basolateral amygdala (BLA). The BLA sends projections to the nucleus basalis magnocellularis (NBM), which in turn sends cholinergic projections to the neocortex. The authors used 100 ng bilateral infusions of 192-Saporin (Cat. #IT-01) in 500 nl 0.1 M PBS to investigate whether lesions of the cholinergic NBM projections affect BLA modulation of memory. 192-Saporin lesions blocked memory enhancement normally induced by norepinephrine infusions into the BLA. This finding suggests NBM-cortex projections may mediate BLA modulation of memory storage or processing in the neocortex.

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

Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M (2002) Isoflurane and nociception: Spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiol 96:367-374. doi: 10.1097/00000542-200202000-00023

Summary: The authors injected 3 µg/3 µl of anti-DBH-SAP (Cat. #IT-03) into the lateral ventricle of rats to determine whether noradrenergic brainstem nuclei and descending spinal pathways are responsible for the antinociceptive actions of isoflurane. The results indicate that isoflurane modulates nociception by as many as three mechanisms, utilizing various combinations of noradrenergic neurons, adrenoceptors, and descending spinal pathways.

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

Safety Instructions

Good laboratory technique must be employed for the safe handling of this product. This requires observation of the following practices:

1. Wear appropriate laboratory attire, including lab coat, gloves and safety glasses.

2. Do not pipet by mouth, inhale, ingest or allow product to come into contact with open wounds. Wash thoroughly any part of the body which comes into contact with the product.

3. Avoid accidental autoinjection by exercising extreme care when handling in conjunction with any injection device.

4. This product is intended for research use by qualified personnel only. It is not intended for use in humans or as a diagnostic agent. Advanced Targeting Systems is not liable for any damages resulting from the misuse or handling of this product.

For disposal: autoclave, or expose to 0.2 M NaOH, materials that come into contact with the toxin.

Q: We’re submitting a protocol to our IACUC to use IB4-SAP (Cat. #IT-10). We plan to inject the targeted toxin and then sacrifice the animal ten days later. What, if any, are the safety issues here?

A: The only danger to lab personnel from IB4-SAP would be accidental self-injection, and even then, at the doses typically used in rats, it would only produce very localized effects at the injection site.

Once injected into animals, the agent is rapidly rendered inaccessible to anyone else by binding, internalization and eventual catabolism. It is extremely unlikely that intact toxin would ever be excreted or recoverable from the rats. The components of the toxin, IB4 and saporin, by themselves are no toxic threat. We use no special precautions with such rats except appropriate care for whatever neurologic deficits they develop, i.e. foot drop, autotomy, etc.

One caveat: To the best of my knowledge the above statements are accurate, but I do not know of any experimental data that directly addresses the issues. I base my comments on our long experience with similar agents including ricin and volkensin which are much more toxic and unstable.

See: Targeted Toxins

Cahill JFX, Baxter MG (2001) Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning. Eur J Neurosci 14:1856-1864. doi: 10.1046/j.0953-816x.2001.01807.x

Summary: The authors compared ibotenic acid (IA)-treated rats with those injected with 45 ng and 30 ng of 192-Saporin (Cat. #IT-01) into two separate coordinates of the medial septum/vertical limb of the diagonal band (MS/VDB) to investigate the role of basal forebrain projections in modulating strategy selection in spatial learning. While rats with IA lesions in the MS/VDB demonstrated significant disruption of the learning process, the 192-Saporin-lesioned rats did not show this effect.

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

Lamprea MR, Cardenas FP, Silveira R, Morato S, Walsh TJ (2000) Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: Forebrain cholinergic mechanisms. Behav Brain Res 117:97-105. doi: 10.1016/s0166-4328(00)00294-1

Summary: 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.

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

Ballmaier M, Casamenti F, Zoli M, Pepeu G, Spano P (2001) Selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis impairs prepulse inhibition of acoustic startle. Neuroscience 108(2):299-305. doi: 10.1016/s0306-4522(01)00413-4

Summary: One of the measures for schizophrenia is a deficit in sensorimotor gating (the ability of the brain to filter sensory input to focus on selective stimuli) measured by prepulse inhibition (PPI) of the startle reflex. The authors injected 300 nl of 400 ng/µl 192-Saporin (Cat. #IT-01) into each side of the nucleus basalis magnocellularis (NBM) in rats to examine the effect of NBM cholinergic neuron elimination on the startle reflex. The data show a significant, persistent disruption of the PPI independent of the amplitude of the startle reflex. This suggests the NBM may play an important role in information processing in schizophrenia.

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

Vogt LJ, Sim-Selley LJ, Childers SR, Wiley RG, Vogt BA (2001) Colocalization of mu-opioid receptors and activated G-proteins in rat cingulate cortex. J Pharmacol Exper Ther 299:840-848.

Summary: The anterior cingulate cortex (ACC) is a primary site of opiate drug action, and much of this activity is associated with the m-opioid receptor (MOR). The mechanisms by which MOR regulates pain in the ACC are not well understood. Using anti-DBH-SAP (7 µg into left lateral ventricle in rat; Cat. #IT-03) the authors mapped MOR activity in the ACC and evaluated the histochemical and behavioral relationships between MOR binding and mu-receptor-activated G-proteins after lesioning.

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

Himmelheber AM, Sarter M, Bruno JP (2001) The effects of manipulations of attentional demand on cortical acetylcholine release. Brain Res Cogn Brain Res 12(3):353-370. doi: 10.1016/s0926-6410(01)00064-7

Summary: Cortical cholinergic afferents from the basal forebrain are suspected to be involved in attentional tasks. Regulatory impairment of these afferents has been hypothesized to contribute to attentional deficits seen in conditions as diverse as Alzheimer’s disease and schizophrenia. The authors have previously shown that 192-Saporin (Cat. #IT-01) lesions result in severe impairments in tasks requiring sustained attentional processing. In these experiments the authors suggest that cell response is dependent on the level of demand. They demonstrate that removal of p75+ cells (0.5 µg/µl bilaterally infused into the nucleus basalis region in rat) impairs sustained attentional performance, but does not impact low-demand task performance.

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

Vulchanova L, Olson TH, Stone LS, Riedl MS, Elde R, Honda CN (2001) Cytotoxic targeting of isolectin IB4-binding sensory neurons. Neuroscience 108(1):143-155. doi: 10.1016/s0306-4522(01)00377-3 PMID: 11738138

Summary: Vulchanova et al. examine the role of IB4-binding neurons in nociception. IB4-SAP (Cat. #IT-10) was injected into rats (2 µg in left sciatic nerve). The resulting ablation of IB4-binding neurons provides evidence for their role in nociceptive processing and demonstrates a rapid compensatory response to signalling of acute pain.

Related Products: IB4-SAP (Cat. #IT-10), Saporin Goat Polyclonal (Cat. #AB-15), Saporin Goat Polyclonal, HRP-labeled (Cat. #AB-15HRP)

Wrenn CC, Wiley RG (2001) Lack of effect of moderate Purkinje cell loss on working memory. Neuroscience 107(3):433-445. doi: 10.1016/s0306-4522(01)00326-8

Summary: When 192-Saporin (Cat. #IT-01) is injected intracerebroventricularly, some p75-expressing cerebellar Purkinje cells are eliminated along with cholinergic neurons. To verify that the effects of basal forebrain lesions on working memory were not caused by loss of these Purkinje cells the authors compared doses of 1 µg OX7-SAP (Cat. #IT-02) and either 2 µg or 4 µg of 192-Saporin injected into the lateral ventricle. The data show that although similar amounts of Purkinje cells were eliminated by OX7-SAP and the lower dose of 192-Saporin, no working memory deficits resulted. Only the 4-µg dose of 192-Saporin produced working memory deficits, they conclude that this is not due to Purkinje cell loss, but the loss of cholinergic neurons.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02)