targeted-toxins

Strichartz G, Khasabov S, Barr T, Wang J, Simone D (2018) Modulation of chronic post-thoracotomy pain by NK-1 neurons in the rostral ventromedial medulla is not paralleled by changes spinal MAPKinase activation. J Pain 19:S14. doi: 10.1016/j.jpain.2017.12.065

Objective: To evaluate SSP-SAP in treatment of tactile hypersensitivity for Chronic Post-Thoractotomy Pain (CPTP).

Summary: SSP-SAP 3 weeks before thoracotomy and rib retraction (TRR) was able to completely prevent CPTP, assayed by tactile hypersensitivity.

Usage: Ablation of Neurokinin-1 receptor (NK-1R)- expressing neurons in the rat rostral ventromedial medulla (RVM), by micro-injection of the specific neurotoxin SSP-SAP.  No effect with treatment of control, Blank-SAP (IT-21).

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Ermine CM, Wright JL, Frausin S, Kauhausen JA, Parish CL, Stanic D, Thompson LH (2018) Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson’s disease and the impact on hippocampal neurogenesis. Hippocampus 28(5):327-337. doi: 10.1002/hipo.22835

Objective: The mechanisms underlying reduced neurogenesis in Parkinson’s Disease (PD) are not well established. The authors tested the hypothesis that noradrenergic and dopaminergic depletion, as occurs in PD, impairs hippocampal neurogenesis.

Summary: Mechanisms of neurotransmitter-based regulation of cognition and hippocampal neurogenesis may well overlap under certain conditions but the present results do not suggest a simple relationship associated with the degeneration of the two most prominently affected transmitter systems in PD.

Usage: Rats received 1 mcg Anti-DBH-SAP icv.

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

Turnbull MT, Boskovic Z, Coulson EJ (2018) Acute down-regulation of BDNF signaling does not replicate exacerbated amyloid-β levels and cognitive impairment induced by cholinergic basal forebrain lesion. Front Mol Neurosci 11:51. doi: 10.3389/fnmol.2018.00051

Objective: To determine if degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of Amyloid beta  pathology and cognitive impairment.

Summary: Lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble Ab levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice. Cognitive decline and Amyloid-beta pathology induced by cholinergic basal forebrain neuron loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission.

Usage: To lesion BFCNs, a single infusion of murine p75-SAP or control rabbit IgG-SAP (0.4 mg/ml) was stereotaxically injected into the basal forebrain.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Zhuravin IA, Dubrovskaya NM, Tumanova NL, Vasilev DS, Nalivaeva NN (2018) Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions. Evolutionary Physiology and Biochemistry – Advances and Perspectives: InTech 714-741. doi: 10.5772/intechopen.73666

Summary: The effectiveness of the studies of the pathogenesis of AD and search for the strategies of its prevention and treatment depend on appropriate modeling of the pathological conditions in the brain leading to AD. Traditionally, the main focus on designing animal models of AD was related to the identification of brain areas and mediator systems related to memory. One model employed injections of a monoclonal antibody against growth factor receptor conjugated with saporin (192 IgG-saporin), which also resulted in the loss of cholinergic neurons and cognitive disorder

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

Arias-Carrion O, Ortega-Robles E, de Celis-Alonso B, Palasz A, Mendez-Rojas MA, Salas-Pacheco J, Murillo-Rodriguez E (2018) Depletion of hypocretin/orexin neurons increases cell proliferation in the adult subventricular zone. CNS Neurol Disord Drug Targets 17:106-112. doi: 10.2174/1871527317666180314115623

Objective: To establish the relationship between the depletion of orexin neurons and the number of proliferating cells in the subventricular zone.

Summary: The adult subventricular zone is affected by orexinergic signaling, the functional implication of which must be further elucidated.

Usage: 90 ng of Orexin-SAP or pyrogen-free saline was stereotaxically injected into the lateral hypothalamus (3.2 caudal, 1.7 lateral to bregma, 8.1 ventral to the skull surface) of male Wistar rats.

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

Wang X, Ma S, Wu H, Shen X, Xu S, Guo X, Bolick ML, Wu S, Wang F (2018) Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition. Exp Mol Med 50(2):e445. doi: 10.1038/emm.2017.271

Objective: To investigate whether the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system.

Summary: MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

Usage: Anti-DAT-SAP was injected i.t. or i.c.v. with ISO-1 alone or ISO-1 combined with one of the other regulators on Day 7 post-nerve injury for 14 days, and pain behaviors, including 50% withdrawal threshold, mechanical pressure and thermal withdrawal latency, were observed throughout the 70 days post nerve injury.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Israel MR, Morgan M, Tay B, Deuis JR (2018) Toxins as tools: Fingerprinting neuronal pharmacology. Neurosci Lett 679:4-14. doi: 10.1016/j.neulet.2018.02.001

Summary: This review article provides an overview of the experimental techniques used to assess the effects that toxins have on neuronal function, as well as discussion on toxins that have been used as tools, with a focus on toxins that target voltage-gated and ligand-gated ion channels.

Related Products: IB4-SAP (Cat. #IT-10), NPY-SAP (Cat. #IT-28)

Araldi D, Khomula EV, Ferrari LF, Levine JD (2018) Fentanyl induces rapid onset hyperalgesic priming: Type I at peripheral and type II at central nociceptor terminals. J Neurosci 38(9):2226-2245. doi: 10.1523/JNEUROSCI.3476-17.2018

Objective: To evaluate priming, at both nociceptor terminals, the effect of local administration of agents that reverse type I (protein translation) or type II [combination of Src and mitogen-activated protein kinase (MAPK)] priming

Summary: Fentanyl, acting at the -opioid receptor (MOR), induces hyperalgesia and hyperalgesic priming at both the central and peripheral terminal of nociceptors and this is mediated by endoplasmic reticulum Ca2 signaling. Priming in the central terminal is type II, whereas that in the peripheral terminal is type I. Our findings may provide useful information for the design of drugs with improved therapeutic profiles, selectively disrupting individual MOR signaling pathways, to maintain an adequate long-lasting control of pain.

Usage: IB4-SAP was diluted in saline and a dose of 3.2 μg in a volume of 20 μl and administered intrathecally 14 d before experiments

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

Park HW, Kim H-L, Park YS, Kim I-B (2018) The transient intermediate plexiform layer, a plexiform layer-like structure temporarily existing in the inner nuclear layer in developing rat retina. Exp Neurobiol 27:28-33. doi: 10.5607/en.2018.27.1.28

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

Lee SJ, Jokiaho AJ, Sanchez-Watts G, Watts AG (2018) Catecholaminergic projections into an interconnected forebrain network control the sensitivity of male rats to diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 314(6):R811-R823. doi: 10.1152/ajpregu.00423.2017

Objective: To investigate the role of hindbrain catecholamine neuron pathways and their contribution to long-term energy homeostasis by controlling obesogenic sensitivity to a high-fat, high sucrose choice diet.

Summary: The authors show that catecholamine neurons (primarily in the VLM and NTS) convey essential feedback signals to enable long-term adaptive control of energy metabolism when animals consume a predominantly carbohydrate diet. This is the first report specifically associating this projection system with the long-term control of adiposity.

Usage: Catecholaminergic projections to the PVH and related parts of the forebrain were lesioned with bilateral injections each consisting of 42 ng/200 nL of Anti-DBH-SAP or equimolar amounts of control Mouse IgG-SAP.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)