targeted-toxins

Seven YB, Mitchell GS (2019) Mechanisms of compensatory plasticity for respiratory motor neuron death. Respir Physiol Neurobiol 265:32-39. doi: 10.1016/j.resp.2019.01.001

Summary: Discusses recent advances in understanding of mechanisms giving rise to compensatory respiratory plasticity in response to respiratory motor neuron death.

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

Koshy Cherian A, Kucinski A, Wu R, deJong IEM, Sarter M (2019) Co-treatment with rivastigmine and idalopirdine reduces the propensity for falls in a rat model of falls in Parkinson’s disease. Psychopharmacology 236:1701–1715. doi: 10.1007/s00213-018-5150-y

Objective: The authors used a longer and more taxing rotating beam apparatus to determine the potential therapeutic efficacy of idalopirdine when combined with rivastigmine.

Summary: The results extend the prediction that the combined treatment with idalopirdine and an AChE inhibitor improves complex movement control and reduces propensity for falls in patients with movement disorders.

Usage: Basal forebrain cholinergic neurons situated in the nucleus basalis and substantia innominata were targeted with 192-IgG-SAP in aCSF infused bilaterally (200 ng/μL; 0.8 μL/hemisphere).

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

Saika F, Kiguchi N, Matsuzaki S, Kobayashi D, Kishioka S (2019) Inflammatory macrophages in the sciatic nerves facilitate neuropathic pain associated with type 2 diabetes mellitus. J Pharmacol Exp Ther 368(3):535-544. doi: 10.1124/jpet.118.252668

Objective: To determine whether inflammatory macrophages contribute to neuropathic pain associated with type 2 diabetes-mellitus (T2DM).

Summary: Inhibitory agents for macrophage-driven neuroinflammation could be potential candidates for novel pharmacotherapy against intractable neuropathic pain.

Usage: Injections of Mac-1-SAP or unconjugated Saporin (10 μl) were administered 3 times every 2 days. Perineural administration of Mac-1-SAP improved high-fat diet (HFD)-induced mechanical allodynia and the accumulation of F4/80+ macrophages and the upregulation of inflammatory mediators in the SCN after HFD-feeding.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Gao ZR, Chen WZ, Liu MZ, Chen XJ, Wan L, Zhang XY, Yuan L, Lin JK, Wang M, Zhou L, Xu XH, Sun YG (2019) Tac1-expressing neurons in the periaqueductal gray facilitate the itch-scratching cycle via descending regulation. Neuron 101(1):45-59.e9. doi: 10.1016/j.neuron.2018.11.010

Objective: To determine the neural mechanism promoting the itch-scratching cycle.

Summary: Ablation of Tac1+ but not SST+ neurons decreases itch-induced scratching behavior. l/vlPAG Tac1+ neurons Induce Scratching Behavior via a Descending Pathway.

Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Control Blank-SAP (400 ng/5 mL).

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Xiong L, Liu Y, Zhou M, Wang G, Quan D, Shen C, Shuai W, Kong B, Huang C, Huang H (2018) Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction. Europace 20(12):2036-2044. doi: 10.1093/europace/euy090

Objective: To evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI).

Summary: Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Usage: 20 μl of CTB-SAP (1.2 mg/ml) was mixed with 4 μl of 3% Evans blue dye to make it visible (CTB-SAP is colorless), ensuring localization within the ganglia. The CTB-SAP/ Evan blue dye solution was slowly and intermittently injected into the left stellate ganglia using a glass micropipette.

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

Ostrin LA, Strang CE, Chang K, Jnawali A, Hung L-F, Arumugam B, Frishman LJ, Smith EL, Gamlin PD (2018) Immunotoxin-induced ablation of the intrinsically photosensitive retinal ganglion cells in rhesus monkeys. Front Neurol 9:1000. doi: 10.3389/fneur.2018.01000

Objective: To develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.

Summary: Findings demonstrated that Melanopsin-SAP was specific for ipRGCs, and induced a graded reduction in the PLR (pupillary light reflex), as well as in ipRGC-driven pupil response with concentration.

Usage: Solutions of 0.316, 1, 3.16, 10, and 50 μg delivered intravitreally.

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

Qiu M, Li J, Tan L, Zhang M, Zhou G, Zeng T, Li A (2018) Targeted ablation of distal cerebrospinal fluid-contacting nucleus alleviates renal fibrosis in chronic kidney disease. Front Physiol 9:1640. doi: 10.3389/fphys.2018.01640

Objective: To test the hypothesis that distal cerebrospinal fluid-contacting nucleus (dCSF-CNs) might affect the renin-angiotensin system (RAS) in kidney injury progression.

Summary: Less CTB-labeled neurons were found in dCSF-CNs of CTB-SAP-treated rats. Meanwhile, CTB-SAP downregulated AGT, Ang II, AT1R, NOX2, catalase, MCP-1, IL-6, fibronectin, and collagen I, and upregulated ACE2 and Mas receptor. Targeted dCSF-CNs ablation could alleviate renal inflammation and fibrosis in chronic kidney injury.

Usage: CTB-SAP (500 ng) into the lateral ventricles over a 3-min period.

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

Seel S, Eacott M, Langston R, Easton A (2018) Cholinergic input to the hippocampus is not required for a model of episodic memory in the rat, even with multiple consecutive events. Behav Brain Res 354:48-54. doi: 10.1016/j.bbr.2017.06.001

Summary: The authors use 192-IgG-SAP (Cat. #IT-01) to examine episodic memory. Continual trials versions of an episodic memory task are unimpaired by cholinergic lesions of the medial septum. In contrast continual trial versions of a location-context (where-which) task are impaired in the same animals. The results replicate the effects of lesions on one-trial a day versions of the same tasks. Increasing the amount of interference between trials by increasing the overlap of features in consecutive events has no effect on the behavioural outcome of these lesions. The result is interpreted in light of models of acetylcholine function centered around pattern separation.

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

Ueda H, Neyama H, Nagai J, Matsushita Y, Tsukahara T, Tsukahara R (2018) Involvement of lysophosphatidic acid-induced astrocyte activation underlying the maintenance of partial sciatic nerve injury-induced neuropathic pain. Pain 159:2170-2178. doi: 10.1097/j.pain.0000000000001316

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

Moreno-Rodriguez M, Martinez-Gardeazabal J, Llorente-Ovejero A, Lombardero L, Manuel I, Rodriguez-Puertas R (2018) Learning and memory improvement mediated by CB1 cannabinoid receptors in animal models of cholinergic dysfunction. Neuroscience 2018 Abstracts 049.05 / S3. Society for Neuroscience, San Diego, CA.

Summary: The selective vulnerability of the basal forebrain cholinergic system (BFCS) is responsible for most of the clinical alterations in learning and memory processes that are characteristic of the Alzheimer’s disease (AD). The loss of cholinergic neurons and muscarinic receptors (MR) in the nucleus basalis of Meynert have been reported in AD. The endocannabinoid system is a neuromodulator of the BFCS, but there are controversial reports regarding the cannabinoid effects in learning and memory processes. The animal models of cholinergic impairment mimic the main histopathological and behavioral effects observed in patients. The MR antagonism, e.g. using scopolamine (SCOP), is used as a model of amnesia in rodents. The intraparenchymal administration of 192-IgG-saporin (SAP) in the nucleus basalis magnocellularis eliminates cholinergic neurons leading to learning and memory deficits. Then, the present study evaluates the modulation of spatial and working memory with the Barnes Maze following a subchronic treatment with a low dose (0.5 mg/kg) of WIN55,212-2 (WIN) in both the SCOP and SAP models of learning and memory deficit. In the SCOP model, the administration of WIN protects learning and memory impairment during the probe trial, recorded as the time spent in the target quadrant (WIN + SCOP: 78 ± 13 sec vs VEH + SCOP: 45 ± 3 sec; p < 0.001). A similar effect of the treatment was observed in the SAP model (SAP: 50 ± 3 sec vs SAP + WIN: 82 ± 7 sec; p < 0.001). This effect was specifically mediated by CB1 receptors, since it was blocked by the co-administration of the specific CB1 antagonist, SR141716A (0.5 mg/kg) (SAP: 49 ± 3 sec vs SAP + WIN + SR: 48 ± 5 sec). However, higher doses of WIN (3 mg/kg) induced negative effects in learning and memory in control (C) rats, but positive and comparable to the lower dose in the SAP model (C: 89 ± 3 sec, C + WIN-3 mg/kg: 48 ± 3 sec; SAP: 49 ± 3; SAP + WIN-3 mg/kg: 80 ± 12 sec; p < 0.001). The CB1 receptor activation by low doses of the cannabinoid agonist WIN are able to block the amnesic effects induced by SCOP and also the learning and memory impairment produced by the BFCS pathway degeneration. CB1 agonists could contribute to improve the clinical symptoms of AD. International application patent PCT/EP2018/054525.

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