targeted-toxins

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)

Kucharczyk MW, Valiente D, Bannister K (2021) Developments in understanding diffuse noxious inhibitory controls: pharmacological evidence from pre-clinical research. J Pain Res 14:1083-1095. doi: 10.2147/JPR.S258602

Summary: This review discusses the pharmacological manipulation interrogation strategies that have been used to examine the functionality of diffuse noxious inhibitory controls (DNIC) and descending control of nociception (DCN).

Usage: Anti-DBH-SAP is one of the drugs tested to influence DNIC expression. They reference a publication that reported that icv injection of Anti-DBH-SAP abolished DCN expression. Anti-DBH-SAP (5 μg/5 μl) was injected in the left ventricle. Lesion of the LC resulted in failure of DNIC, an effect that mimics what is observed behaviorally after chronic TBI.

See: Irvine KA et al. Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue. Exp Neurol 333:113428, 2020.

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

Han W, de Araujo IE (2021) Dissection and surgical approaches to the mouse jugular-nodose ganglia. STAR Protocols 2(2):100474. doi: 10.1016/j.xpro.2021.100474

Usage: Injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.

Related Products: CCK-SAP (Cat. #IT-31)

For complete details on the use and execution of this protocol, please refer to Han et al.

See Also: Han W et al. A neural circuit for gut-induced reward. Cell 175:665-678, 2018.

Liu Y, Forsythe P (2021) Vagotomy and insights into the microbiota-gut-brain axis. Neurosci Res 168:20-27. doi: 10.1016/j.neures.2021.04.001

Objective: To review the use of vagotomy as a tool to explore the role of the vagus nerve in gut to brain signaling.

Summary: This review article is a summary of the knowledge gained from vagotomy, a surgical procedure that involves removing part of the vagus nerve. The article discusses using CCK-SAP to specifically ablate afferent vagal nerves in the gastrointestinal tract.

Usage: The article references a study by Diepenbroek et al. that used CCK-SAP in the following dosages: In vitro: each well was treated with a different dose of saporin conjugates (0, 2.4, 24, or 240 ng) for 24 h. In vivo: An equal volume (rat: 1 µl; mouse: 0.5 µl) of CCK-SAP (250 ng/µl) or Saporin (250 ng/µl) was injected at two sites rostral and caudal to the laryngeal nerve branch.

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

See Also:

• Diepenbroek C et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352, 2017.

Wang Y, Tan B, Wang Y, Chen Z (2021) Cholinergic signaling, neural excitability, and epilepsy. Molecules 26(8):2258. doi: 10.3390/molecules26082258

Summary: In this review, the authors briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability and epilepsy. intraventricular administration of 192-IgG-SAP, which inhibits cholinergic projection to the hippocampus and cortex respectively, facilitates seizure induced by amygdala kindling

Usage: Ferencz et al. used 192-IgG-SAP (2.5 μg icv) to investigate the effect of eliminating cholinergic projections to the hippocampal formation and cerebral cortex on the induction of epilepsy through electrical stimulation of the rat brain. They determined that the loss of specific projections to the amygdala accelerates development of seizures.

See: Ferencz I et al. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats. Eur J Neurosci 12:2107-2116, 2000.

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

Liu X, Wang Y, Tao T, Zeng L, Wang D, Wen Y, Li Y, Zhao Z, Tao A (2021) GRPR/extracellular signal-regulated kinase and NPRA/extracellular signal-regulated kinase signaling pathways play a critical role in spinal transmission of chronic itch. J Invest Dermatol 141(4):863-873. doi: 10.1016/j.jid.2020.09.008

Summary: This study investigates whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. Bombesin-SAP completely abolished extracellular signal-regulated kinase (ERK) activation. ERK was the most highly activated by their agonists BNP (Nppb, brain-derived natriuretic peptide) and octreotide. Nppb-SAP only partially reduced pERK in cervical spinal cord.

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