targeted-toxins

Song SY, Zhang LC (2018) The establishment of a CSF-contacting nucleus “knockout” model animal. Front Neuroanat 12:22. doi: 10.3389/fnana.2018.00022

Objective: To establish a cerebrospinal fluid (CSF)-contacting nucleus-deficient model animal using cholera toxin B subunit-saporin (CTB-SAP).

Summary: The complete ablation occurred by Day 7 after CTB-SAP microinjection. A model animal that had no CSF-contacting nucleus was established after survival beyond that time point. No obvious effects were observed in the vital status of the model animals, and their survival was ensured. The common physiological parameters of model animals were stable. The present study provides a method to establish a CSF-contacting nucleus “knockout” model animal, which is similar to a gene knockout model animal for studying this particular nucleus in vivo.

Usage: 3 μl (500 ng) CTB-SAP was microinjected into the lateral ventricle.

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

Patrone LGA, Biancardi V, Marques DA, Bícego KC, Gargaglioni LH (2018) Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats. J Physiol 596(15):3299-3325. doi: 10.1113/JP275731

Objective: To determine the role of the brainstem CA system in ventilatory control under normocapnic and hypercapnic conditions during different phases of development (P7-8, P14-15 and P20-21) in male and female Wistar rats.

Summary: Brainstem CA neurones produce a tonic inhibitory drive that affects breathing frequency in P7-8 rats and provide an inhibitory drive during hypercapnic conditions in both males and females at P7-8 and P14-15.

Usage: Anti-DBH-SAP (420 ng/μL – 1 μL for P0-1; 1.5 μL for P7-8; 2.0 μL for P13-14) was injected into the 4th ventricle of neonatal Wistar rats of both sexes. Control rats were injected with vehicle (PBS, 0.01 M, pH 7.4) or unconjugated saporin (Cat. #PR-01), with respective volumes for each age, as described for the Anti-DBH-SAP group. All injections were performed using a microinjector pump over a period of 5 min to allow drug diffusion.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

Doyle S, Baker KL, Cunningham C, Lowry JP (2018) Real‐time electrochemical monitoring of choline during systemic inflammation in the freely‐ moving mouse. Monitoring Molecules in Neuroscience . 17th International Conference, Oxford, UK

Summary: The loss of cholinergic innervation (mu p75‐SAP lesion in the basal forebrain) abolished the scopolamine‐induced choline increase in the hippocampus.

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

Huang J, Polgár E, Solinski HJ, Mishra SK, Tseng PY, Iwagaki N, Boyle KA, Dickie AC, Kriegbaum MC, Wildner H, Zeilhofer HU, Watanabe M, Riddell JS, Todd AJ, Hoon MA (2018) Circuit dissection of the role of somatostatin in itch and pain. Nat Neurosci 21(5):707-716. doi: 10.1038/s41593-018-0119-z

Objective: To determine the role of somatostatin in itch and pain.

Summary: Results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.

Usage: Ablation of Npr1- and GRPR-expressing spinal cord interneurons was accomplished by intrathecal (segment L3/4) injection of Nppb-SAP (4 μg/10 μL) and Bombesin-SAP (2.5 μg) respectively.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69)

Lee S, Shi XQ, Fan A, West B, Zhang J (2018) Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain. Mol Pain 14:1744806918764979. doi: 10.1177/1744806918764979

Summary: Depletion of spinal microglia with Mac-1-SAP was able to prevent and reverse neuropathic pain behavior.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

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)