targeted-toxins

Ramezani F, Salehian S, Hosseinzadeh S, Mahjour Z, Babajani T, Ghorbanian D, Feizi F, Pourbagher R (2022) Serotonin-1A receptor activation in the median raphe nucleus improves response learning-based strategy in 192IgG saporin-induced cognitive impairments. Eur J Pharmacol 918:174774. doi: 10.1016/j.ejphar.2022.174774 PMID: 35077674

Objective: Study the effects of median raphe nucleus serotonin-1A autoreceptors stimulation on rats.

Summary: Rats treated with 192-IgG-SAP were put into a Morris maze and studied for spatial cognition. Treated rats offered a proxy for cognitive impairment that directly mimics some features of neurodegeneration in Alzheimer’s disease. Results strongly suggest the involvement of the serotonergic system in spatial navigation.

Usage: Selective cholinergic denervation was achieved by intra-cerebroventricular administration of the 192-IgG-SAP (1.0 μl/each ventricle at the rate of 0.2 μl/min ) on male Wistar rats.

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

McDonough KE (2022) Maintenance mechanism of nociplastic pain in males. University of Texas Medical Branch Thesis.

Objective: The objective of this dissertation is to elucidate the sex-specific mechanisms underlying the transition to and maintenance of a nociplastic pain state using animal models.

Summary: This PhD dissertation investigates the mechanisms underlying the transition from acute to chronic nociplastic pain using murine models. The study finds that in males, spinal microglial activation driven by GABAergic disinhibition allows normally innocuous stimulation to induce a transition to nociplastic pain maintained by spinal microglia and proinflammatory cytokines.

Usage: Intrathecal injection of Saporin or Mac-1-SAP at 8.85 μM.

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

Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2022) Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184. doi: 10.3390/toxins14030184 PMID: 35324681

Summary: Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.

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Xu L, Füredi N, Lutter C, Geenen B, Pétervári E, Balaskó M, Dénes Á, Kovács KJ, Gaszner B, Kozicz T (2022) Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats. Neuropharmacology 205:108898. doi: 10.1016/j.neuropharm.2021.108898

Objective: To show that leptin bound to neurons of the Edinger-Westphal nucleus (EWcp) stimulated STAT3 phosphorylation and increases urocortin 1 (Ucn1)-production in a time-dependent manner.

Summary: EWcp/LepRb/Ucn1 neurons respond to leptin signaling as well as control white adipose tissue size and fat metabolism without altering food intake.

Usage: Ablation of EWcp leptin receptor (LepRb) positive neurons with leptin-saporin. Either unconjugated saporin (53 ng in 80 nl MQ, or Leptin-SAP (90 ng in 80 nl MQ, was injected into the rat midbrain.

Related Products: Leptin-SAP (Cat. #IT-47), Saporin (Cat. #PR-01)

Ujvári B, Pytel B, Márton Z, Bognár M, Kovács LÁ, Farkas J, Gaszner T, Berta G, Kecskés A, Kormos V, Farkas B, Füredi N, Gaszner B (2022) Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat. J Neuroinflammation 19(1):31. doi: 10.1186/s12974-022-02399-w

Objective: To investigate whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

Summary: Neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.

Usage: Leptin-SAP or unconjugated Saporin (0.08 μl) was injected into the EWcp area. This selective ablation of UCN1 neurons was used to validate the depression-like phenotype in rats. Behavioral, functional–morphological, biochemical and histopathological tools were used to test the motor coordination, mood status as well as morphological changes in the brain.

Related Products: Saporin (Cat. #PR-01), Leptin-SAP (Cat. #IT-47)

Barros JFF, Sant’Ana AMS, Dias LC, Murashima AAB, Silva LECMD, Fantucci MZ, Rocha EM (2022) Comparison of the effects of corneal and lacrimal gland denervation on the lacrimal functional unit of rats. Arq Bras Oftalmol 85(1):59-67. doi: 10.5935/0004-2749.20220008

Summary: This study compared the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland.

Usage: Rats received 2.5 μg of 192-IgG-SAP (Cat. #IT-01) directly into the left extraorbital lacrimal gland.

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

See Also:

• Aicher S et al. Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease. Invest Ophthalmol Vis Sci 56:6981-6989, 2015.

Hankerd K (2021) Female-specific mechanisms of nociplastic pain in murine model. The University of Texas Medical Branch at Galveston, Dept Neuroscience Thesis.

Objective: To study nociplastic pain the authors developed a murine model in which postinjury thermal stimulation of injured area triggers the transition to a nociplastic pain state more readily in females.

Summary: Postinjury stimulation of an injured area triggers the transition from transient pain to nociplastic pain, females are more susceptible to this transition, and allyl isothiocyanate -sensitive afferents at the previously injured area maintain the nociplastic pain state in a female gonadal hormone-dependent manner.

Usage: Intrathecal injection of Mac-1-SAP (IT-06) 8.85 mM in mice.

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

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Borkowski LF, Keilholz AN, Smith CL, Canda KA, Nichols NL (2021) Nonsteroidal anti-inflammatory drug (ketoprofen) delivery differentially impacts phrenic long-term facilitation in rats with motor neuron death induced by intrapleural CTB-SAP injections. Exp Neurol 347:113892. doi: 10.1016/j.expneurol.2021.113892

Objective: To determine the effect of ketoprofen delivery on enhanced phrenic long-term facilitation (pLTF)

Summary: pLTF was surprisingly attenuated in 7d CTB-SAP rats and enhanced in 28d CTB-SAP rats (both p < 0.05) following ketoprofen delivery.

Usage: Rats received bilateral intrapleural injections of CTB-SAP; 25 μg dissolved in PBS.

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

Sanna F, Bratzu J, Angioni L, Pina Sorighe M, Cocco C, Argiolas A, Melis MR (2021) Oxytocin-conjugated saporin injected into the substantia nigra of male rats alters the activity of the nigrostriatal dopaminergic system: A behavioral and neurochemical study. Brain Res 1773:147705. doi: 10.1016/j.brainres.2021.147705 PMID: 34744015

Objective: To investigate the effects of Oxytocin-SAP in the substantia nigra of male rats, and assess its impact on nigral Tyrosine Hydroxylase-immunoreactivity, dopamine content, locomotor activity, rotational turning, and striatal dopamine function.

Summary: Researchers investigated the effects of injecting oxytocin-conjugated Saporin into the substantia nigra of male rats. They found that this treatment led to changes in the activity of the nigrostriatal dopaminergic system, as evidenced by alterations in behavior and neurochemical markers associated with dopamine function.

Usage: Oxytocin-SAP (60 ng/μl and 120 ng/μl) was injected unilaterally into the substantia nigra of male rats, respectively, compared to Blank-SAP.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Thorsdottir DJ (2021) The role of BDNF-mediated neuroplasticity in cardiovascular regulation within the hypothalamus and brainstem. Univ Vermont, Dept Pharmacology 1387Thesis.

Summary: This PhD dissertation to determine the mechanism behind BDNF-mediated cardiovascular regulation.

Usage: Rats received bilateral NTS injections of vehicle or Anti-DBH-SAP, which selectively lesions catecholaminergic neurons. Treatment increased blood pressure in the GFP group but failed to affect blood pressure in the BDNF group.

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