targeted-toxins

Alvarez P, Chen X, Bogen O, Green PG, Levine JD (2012) IB4(+) nociceptors mediate persistent muscle pain induced by GDNF. J Neurophysiol 108(9):2545-2553. doi: 10.1152/jn.00576.2012

Summary: GDNF is found in skeletal muscle and can trigger mechanical hyperalgesia. The authors administered a 3.2-μg intrathecal dose of IB4-SAP (Cat. #IT-10) to rats. Loss of the IB4(+) nociceptors led to decreased hyperalgesic priming as well as a reduction in GDNF-induced hyperalgesia. These data indicate that GDNF plays a role in mediating induction of pain.

Related Products: IB4-SAP (Cat. #IT-10)

Koppen JR, Winter SS, Stuebing SL, Cheatwood JL, Wallace DG (2013) Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function. Brain Struct Funct 218(5):1099-1114. doi: 10.1007/s00429-012-0449-7

Summary: Both mnemonic and spatial processing are adversely affected by dementia due to Alzheimer’s disease. There is evidence to support the involvement of cholinergic systems in this deficit. In this work the authors examined how GABAergic neurons in the septohippocampus contribute to these cognitive functions. Rats received a total of 350 ng of GAT-1-SAP (Cat. #IT-32) infused into the medial septum-diagonal band of Broca. Although lesioned animals performed normally in tasks involving spatial cues, food hoarding was affected indicating that self-movement cue processing was interfered with by the loss of these GABAergic neurons.

Related Products: GAT1-SAP (Cat. #IT-32)

Lemons LL, Wiley RG (2012) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation. Neuroscience 216:158-166. doi: 10.1016/j.neuroscience.2012.04.006 PMID: 22522467

Objective: To determine the role of dorsal horn Y1R-expressing neurons in pain.

Summary: Lumbar intrathecal NPY-SAP (1) reduced Complete Freund’s Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia.

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

Savage S, Mattsson A, Olson L (2012) Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons. Neuroscience 216:38-45. doi: 10.1016/j.neuroscience.2012.04.064

Summary: Phenylcyclidine (PCP) has been used to model aspects of schizophrenia in animals. 81 ng of 192-IgG-SAP (Cat. #IT-01) was injected into the nucleus basalis magnocellularis of rats to assess the effects of low dose PCP in a cholinergically-deprived system. Saporin (Cat. #PR-01) was used as a control. Results demonstrate basalocortical cholinergic neurons are necessary for PCP to have full effect.

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

Gil-Bea FJ, Gerenu G, Aisa B, Kirazov LP, Schliebs R, Ramirez MJ (2012) Cholinergic denervation exacerbates amyloid pathology and induces hippocampal atrophy in Tg2576 mice. Neurobiol Dis 48(3):439-446. doi: 10.1016/j.nbd.2012.06.020

Summary: The hallmarks of Alzheimer’s disease (AD) include hippocampal cell loss, cholinergic dysfunction, amyloid plaques, and neurofibrillary tangles, among other things. This work sought to examine the interaction between cholinergic denervation, amyloid precursor protein (APP) processing, and hippocampal integrity. Tg2576 transgenic mice received 2 μg of mu p75-SAP (Cat. #IT-16) injected into the third ventricle. These mice overexpress a version of human APP. Lesioned animals displayed various aspects of AD such as hippocampal synaptic pathology and neurodegeneration, indicating that immunolesions in this mouse line produce a viable model for AD.

Related Products: mu p75-SAP (Cat. #IT-16)

Parent M, Bedard MA, Aliaga A, Soucy JP, Landry St-Pierre E, Cyr M, Kostikov A, Schirrmacher E, Massarweh G, Rosa-Neto P (2012) PET imaging of cholinergic deficits in rats using [(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV). Neuroimage 62(1):555-561. doi: 10.1016/j.neuroimage.2012.04.032

Summary: In order to better understand and evaluate neurodegenerative diseases imaging agents are necessary to visualize the affected systems. [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) is one such agent that shows promise for labeling the vesicular acetylcholine transporter with positron emission tomography. The authors injected 0.2 μg of 192-IgG-SAP (Cat. #IT-01) into the left hemisphere of rats to model cholinergic terminal loss as seen in aged animals. Loss of these terminals was found to reduce [18F]FEOBV binding in the ventral frontal cortex on the lesioned side, and also in the homologous region of the contralateral hemisphere, allowing detection of both physiological and pathological reduction of cholinergic terminals.

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

Huang TY, Lin LS, Cho KC, Chen SJ, Kuo YM, Yu L, Wu FS, Chuang JI, Chen HI, Jen CJ (2012) Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum. J Appl Physiol 113(6):889-895. doi: 10.1152/japplphysiol.01363.2011

Summary: It is known that exercise can improve motor performance, but the cellular changes that occur in the cerebellum in response to exercise are not understood. Rats were subject to exercise training and a rotarod test was used to evaluate performance. After training some animals were given a 2 μg injection of OX7-SAP (Cat. #IT-02) into the lateral ventricle. In sedentary rats OX7-SAP administration reduced rotarod performance as well as eliminated 60% of Purkinjie cells. Rats given exercise training exhibited much milder injury in the cerebellum as a result of the lesion and maintained a higher level of rotarod performance than the sedentary group.

Related Products: OX7-SAP (Cat. #IT-02)

Laplante F, Zhang ZW, Huppe-Gourgues F, Dufresne MM, Vaucher E, Sullivan RM (2012) Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats. Neuropharmacology 63(6):1075-1084. doi: 10.1016/j.neuropharm.2012.07.033

Summary: Current thought is that loss of cholinergic function in the nucleus accumbens (N.Acc) is associated with schizophrenia. This deficit is accompanied by low dopaminergic activity in the prefrontal area, which adversely affects working memory. Rats received bilateral injections totaling 500 ng of anti-ChAT-SAP (Cat. #IT-42) into the N.Acc; rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals had markedly reduced mesocortical dopamine activation, which corresponded with cognitive impairments. The data suggest that loss of cholinergic neurons in the N.Acc causes loss of dopamine function in the mesocorticolimbic system.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Q: Recently, I attended a talk where the speaker said that a targeted toxin was able to work when an antagonist did not. Can you explain how your technology is different?

A: Certainly. It is a very interesting question and one that helps explain the Targeting Technology quite well. An antagonist is used to block a receptor on a cell to keep it from binding a target molecule and activating the cell. For example, a substance P antagonist binds to the substance P (NK-1) receptor. The hypothesis was that if the antagonist binds to the receptor, substance P cannot bind and the cell will not be activated. The reality is that there are other receptors besides the substance P receptor on that cell. If any of these other receptors bind to their target molecules, then the cell will still be activated.

It sometimes is not enough to block one particular receptor. The ATS targeting technology (molecular surgery) can use any of these cell surface receptors to target and completely eliminate the cell. That way, there are no receptors left to bind; no cell left to be activated. Importantly, molecular surgery cleanly removes one particular cell type and does not damage bystander cells. Once the debris from the targeted cell is cleared away, there is nothing remaining to interfere or affect the normal action/interaction of other cells.

Related Products: Targeted Toxins

Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087-1187 . doi: 10.1152/physrev.00032.2011

Summary: This review summarizes mechanisms in the brain that control sleep and wakefulness. Areas discussed include wakefulness promoting systems, non-REM sleep and REM sleep definitions, the function of each kind of sleep, and dysfunction that occurs as a result of sleep disruption. Several targeted conjugates are mentioned, such as 192-IgG-SAP (Cat. #IT-01), anti-DBH-SAP (Cat. #IT-03), and orexin-SAP (Cat. #IT-20). The review summarizes the use of these products to better understand sleep networks.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)