targeted-toxins

Ku SK, Lim JM, Cho HR, Bashir KMI, Kim YS, Choi JS (2021) Tart cherry (fruit of prunus cerasus) concentrated powder (tccp) ameliorates glucocorticoid-induced muscular atrophy in mice. Medicina (Kaunas) 57(5):485. doi: 10.3390/medicina57050485 PMID: 34066110

Summary: Tart cherries have shown memory impairment lowering properties.

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

See Also:

• Matchynski JJ et al. Combinatorial Treatment of Tart Cherry Extract and Essential Fatty Acids Reduces Cognitive Impairments and Inflammation in the mu-p75 Saporin-Induced Mouse Model of Alzheimer’s Disease. J Med Food 16(4):288-295, 2013.

Kawanabe R, Yoshihara K, Hatada I, Tsuda M (2021) Activation of spinal dorsal horn astrocytes by noxious stimuli involves descending noradrenergic signaling. Mol Brain 14(1):79. doi: 10.1186/s13041-021-00788-5

Summary: Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). Astrocytes in the spinal dorsal horn (SDH) increase intracellular Ca2+ levels following intraplantar injection of the noxious irritant, formalin, however the underlying mechanisms remain unknown. The authors investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic). Activation of α1A-adrenaline receptors via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca2+ responses in the SDH evoked by noxious stimuli, including chemical irritants

Usage: Intrathecal treatment with Anti-DBH-SAP, which kills SDH-projecting NAergic neurons, attenuates formalin pain (5.0 µg/20 µl; Martin et al., 1999)

See: Martin WJ et al. Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing. Pain 80:57-65, 1999.

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

Kim HN, Kim JY (2021) A systematic review of oropharyngeal dysphagia models in rodents. Int J Environ Res Public Health 18(9):4987. doi: 10.3390/ijerph18094987

Objective: To organize the rodent models of oropharyngeal dysphagia reported to date.

Summary: Applying and analyzing the treatment in rodent models of dysphagia induced from various causes is an essential process to develop symptom-specific treatments. The results of this study provide fundamental and important data for selecting appropriate animal models to study dysphagia.

Usage: CTB-SAP treated rats exhibited targeted hypoglossal motor neuron death; decreased hypoglossal motor output; and swallowing and lick deficits.

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

da Costa C, Soares JI, Lukoyanov NV (2021) Forebrain cholinergic plasticity in rats with chronic epilepsy induced by status epilepticus. . 14th U.PORTO Young Researchers Meeting

Summary: This poster had the following aims: 1) Evaluate the GABAergic population in the MS/DB in a chronic epilepsy model of kainic acid (KA)-treated rats. 2) Assess the GABAergic and cholinergic interconnectivity in the MS/DB in a chronic epilepsy model of kainic acid (KA)-treated rats. Results showed that outcomes were improved in rats receiving 192-IgG-SAP treatment as compared to Sham. Mortality: Sham – 50%; SAP – 0%.Recurrent motor seizures: Sham – 83%; SAP – 40%. Recurrent motor + EEG seizures: Sham – 100%; SAP – 50%.

Usage: 192-IgG-SAP was used to produce a moderate, but significant loss of septohippocampal cholinergic cells and to suppress their plasticity.

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

Ming X, Prasad N, Thulasi V, Elkins K, Shivamurthy VKN (2021) Possible contribution of cerebellar disinhibition in epilepsy. Epilepsy Behav 118:107944. doi: 10.1016/j.yebeh.2021.107944

Summary: The authors hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. An animal study showed microinjection of SSP-SAP produced a selective ablation of hippocampal inhibitory interneurons in vivo and a highly focal disinhibition. These results also demonstrate that the ‘‘epileptic” pathophysiology produced by experimental status epilepticus or head trauma can be replicated by focal interneuron loss, without involving principal cell loss and other interpretive confounds inherent in the use of global neurologic injury models.

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

See Also:

• Martin JL et al. Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of substance P. J Comp Neurol 436:127-152, 2001.
• Chun E et al. Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57, 2019.

Madrid LI, Jimenez-Martin J, Coulson EJ, Jhaveri DJ (2021) Cholinergic regulation of adult hippocampal neurogenesis and hippocampus-dependent functions. Int J Biochem Cell Biol 134:105969. doi: 10.1016/j.biocel.2021.105969

Summary: In this review, the authors appraise the evidence linking the contribution of cholinergic signalling to the regulation of adult hippocampal neurogenesis and hippocampus-dependent functions.

Usage: A hallmark feature of all basal forebrain cholinergic neurons is the expression of high levels of the p75 neurotrophin receptor which can be precisely targeted using 192-IgG-SAP. Administration of 192-IgG-SAP (icv, 2.5 µg, Mohapel et al., 2005) resulted in significant impairment in adult hippocampal neurogenesis in rats. In contrast, a study which lesioned MS cholinergic neurons in mice reported no effect on baseline proliferation in the hippocampus. Mice received 3.6 µg of mu p75-SAP into each lateral ventricle (Ho et al., 2009). Although the number of surviving neurons was similar in both lesioned and control animals, most of the progenitor cells in the lesioned animals could not survive without cholinergic input.

Related Products: 192-IgG-SAP (Cat. #IT-01), mu p75-SAP (Cat. #IT-16)

See Also:

• Mohapel P et al. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. Neurobiol Aging 26:939-946, 2005.
• Ho NF et al. Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice. BMC Neurosci 10:57, 2009.

Loftén A, Adermark L, Ericson M, Söderpalm B (2021) An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol’s dopamine-releasing effect. Addict Biol 26(3):e12959. doi: 10.1111/adb.12959

Summary: Basal extracellular levels of dopamine within the nucleus accumbens are not sustained by muscarinic acetylcholine, whereas accumbal Cholinergic interneurons-ACh are involved in mediating ethanol-induced dopamine release.

Usage: Anti-ChAT-SAP or Rabbit IgG-SAP were infused at a flow rate of 0.05 μl/min for 10 min giving a total volume of 0.5 μl.

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

De Pontia G (2021) Exploring early therapeutic approaches in a mucopolysaccharidosis type I (MPSI) mouse model. Univ Milan-Bicocca Thesis.

Objective: Author applied hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) treatments, individually or in combination, during the neonatal period, to evaluate the outcomes in a Mucopolysaccharidosis type I (MPS-I) mouse model.

Summary: Although the impact of the immune response on the outcome remains unknown and debated, authors demonstrated that the combination therapy permitted immune tolerance, avoiding anti-IDUA antibody development. Taken together, the data demonstrate that the combination of HSCT and ERT at a neonatal age may represent a beneficial therapeutic option for patients with MPS-I.

Usage: Using both CD45-SAP and/or CD117-SAP resulted in depletion capability similar to Total body irradiation (TBI) and stable unbiased high donor chimerism in adult immunocompetent mice, with architectural maintenance and reduced toxicity.

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.

Pethe P, Kale V (2021) Placenta: A gold mine for translational research and regenerative medicine. Reprod Biol 21(2):100508. doi: 10.1016/j.repbio.2021.100508

Objective: To review recent studies regarding the therapeutic potential of human placenta-derived mesenchymal stromal/stem cells (hPMSCs) and their extracellular vesicles (EVs).

Summary: These studies demonstrate salutary effects of hPMSC-EVs on a range of different difficult-to-treat conditions like Duchenne Muscular Dystrophy, Parkinson’s disease, acute kidney injury, etc., and therefore, it is imperative that these leads should be taken forward to clinical trials.

Usage: 8 µL of 192 IgG-saporin (0.63 µg/µL) were bilaterally injected into the ventricle to induce a dementia rat model.

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

Marques SM, Naves LM, Silva TME, Cavalcante KVN, Alves JM, Ferreira-Neto ML, de Castro CH, Freiria-Oliveira AH, Fajemiroye JO, Gomes RM, Colombari E, Xavier CH, Pedrino GR (2021) Medullary noradrenergic neurons mediate hemodynamic responses to osmotic and volume challenges. Front Physiol 12:649535. doi: 10.3389/fphys.2021.649535

Summary: The study sought to determine the role of noradrenergic neurons in hypertonic saline infusion (HSI)-induced hemodynamic recovery. Findings show that together the A1 and A2 neurons are essential to HSI-induced cardiovascular recovery in hypovolemia.

Usage: Medullary catecholaminergic neurons were lesioned by nanoinjection of Anti-DBH-SAP (0.105 ng·nl−1) into A1, A2, or both (LES A1; LES A2; or LES A1+A2, respectively). Sham rats received nanoinjections of unconjugated saporin in the same regions.

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