References

Yaksh TL, dos Santo G, Lemes J, Malange K (2023) Neuraxial drug delivery in pain management: An overview of past, present, and future. Anaesthesiology doi: 10.1016/j.bpa.2023.04.003

Objective: Activation of neuraxial nociceptive linkages leads to a high level of encoding of the message that is transmitted to the brain and that can initiate a pain state with its attendant emotive covariates. The authors review the encoding of this message and describe the how it is subject to regulation by pharmacological targeting of dorsal root ganglion and dorsal horn systems.

Summary: Authors provide an overview of the past, present and future directions of the biology, pharmacology and technology relevant to the use of the neuraxial route. SP-SAP was used as a neuraxial toxin to eliminate NK1R expressing cells, which characteristic of neurons known to be the second order neurons responding to C fiber input. Delivery of SP-SAP results in long-lasting loss of NK1 bearing dorsal horn neurons and analgesia.

Related Products: SP-SAP (Cat. #IT-07)

Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096

Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.

Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.

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

See Also:

• Dornan WA et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav Brain Res 82:93-101, 1996.

Konturek-Ciesla A, Dhapola P, Zhang Q, Säwén P, Wan H, Karlsson G, Bryder D (2023) Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age. Cell Rep 42(4):112304. doi: 10.1016/j.celrep.2023.112304 PMID: 36961818

Objective: Using single-cell transcriptome and epitope profiling to study hematopoiesis and the effects from aging.

Summary: The contribution from Hematopoietic stem cells (HSCs) to mature blood cells decline with age. The authors used transcriptome and epitope profiling to reconstruct early hematopoiesis and assessed HSC-specific lineage tracing. Their analysis identified previously uncharacterized cell populations which included multipotent progenitor cells (MPP) Ly-1 and Ly-II. Flt3 is a marker indicative of early differentiation found on MPP cells and was targeted for elimination via an antibody to Flt3 combined with Streptavidin-ZAP. This cell depletion provided evidence for the lack of self-renewal of Ly-1 and Ly-II cells in a transplantation setting and suggests that they need to be continuously replenished by upstream HSPCs.

Usage: Biotinylated anti-CD135 (clone A2F10) was combined with Streptavidin-ZAP at a 1:1 molar ratio, diluted in PBS to 0.2 mg/ml and injected into mice at 3 mg/kg.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2023) Streptavidin-saporin: Converting biotinylated materials into targeted toxins. Toxins 15(3):181. doi: 10.3390/toxins15030181

Summary: This manuscript describes the myriad of ways Streptavidin-ZAP is used and how this technology supports the scientific process of ‘Molecular Surgery’ and progress in research and drug development. Insights from publications and research performed using Streptavidin-ZAP and its impact on academia and industry for research and drug development are presented.

Read the full article.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326

Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.

Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Kim S, Shukla RK, Yu H, Baek A, Cressman SG, Golconda S, Lee GE, Choi H, Reneau JC, Wang Z, Huang CA, Liyanage NPM, Kim S (2022) CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells. Front Immunol 13:1011190. doi: 10.3389/fimmu.2022.1011190

Objective: To use a new murine testing model to demonstrate a substantial enrichment of tissue-resident Foxp3+ Tregs following CD3e-IT treatment.

Summary: The multi-organ pharmacodynamics of CD3e-IT and potential treatment resistance mechanisms identified in this study may generate new opportunities to further improve this promising treatment.

Usage: Male C57BL/6J mice were injected into retro-orbital sinus with 15 μg S-CD3e-IT (Biotinylated Anti-CD3 mixed with Streptavidin-ZAP in sterile 200 μl PBS twice a day for four consecutive days.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Brock O, Gelegen CE, Sully P, Salgarella I, Jager P, Menage L, Mehta I, Jęczmień-Łazur J, Djama D, Strother L, Coculla A, Vernon A, Brickley S, Holland P, Cooke S, Delogu A (2022) A role for thalamic projection GABAergic neurons in circadian responses to light. J Neurosci doi: 10.1523/JNEUROSCI.0112-21.2022 PMID: 36280260

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38), Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Bochi APG, Ferreira GDS, Del Bianco V, Pinto PR, Rodrigues LG, Trevisani MDS, Furukawa LNS, Bispo KCS, da Silva AA, Velosa APP, Nakandakare ER, Machado UF, Teodoro WPR, Passarelli M, Catanozi S (2022) Aerobic exercise training reduces atherogenesis induced by low-sodium diet in LDL receptor knockout mice. Antioxidants (Basel) 11(10):2023. doi: 10.3390/antiox11102023 PMID: 36290746

Objective: To investigate the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet.

Summary: AET counteracts the deleterious effects of chronic LS diet in atherogenesis by reducing peripheral insulin resistance, lipid infiltration, carboxymethyllysine, receptor for advanced glycation end products, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk in LDL receptor knockout mice.

Usage: IF staining (1:50)

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Yang R, Gao Y, Li H, Huang W, Tu D, Yang M, Liu X, Hong JS, Gao HM (2022) Posttranslational S-nitrosylation modification regulates HMGB1 secretion and promotes its proinflammatory and neurodegenerative effects. Cell Rep 40(11):111330. doi: 10.1016/j.celrep.2022.111330 PMID: 36103834

Objective: To demonstrate that S-nitrosylation (SNO) is essential and sufficient for inflammation-elicited HMGB1 secretion.

Summary: Results indicate crucial roles for SNO modification in HMGB1 secretion and HMGB1-Mac1 interaction for inflammatory neurodegeneration, identifying a mechanistic basis for Parkinson’s Disease development.

Usage: Confocal double-label immunofluorescence (1:1000)

Related Products: NO-L-Cysteine Mouse Monoclonal, Conjugated (Cat. #AB-T125)

Lee W, Song G, Bae H (2022) Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells. Antioxidants (Basel) 11(9):1714. doi: 10.3390/antiox11091714

Objective: To determine the effects of laminarin on pancreatic cancer.

Summary: Laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for pancreatic ductal adenocarcinoma (PDAC) with potential as a treatment for PDAC.

Usage: Lund et al. work on 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin Anti-CD105-SAP.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

See Also:

• Lund K et al. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185, 2017.

Madrid LI, Bandhavkar S, Hafey K, Jimenez-Martin J, Milne M, Coulson EJ, Jhaveri DJ (2022) Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis. bioRxiv 2022.08.25.505357. doi: 10.1101/2022.08.25.505357

Objective: To investigate the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippocampus and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons.

Summary: This work reveals stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippocampal neurogenesis.

Usage: Medial septum cholinergic lesion was achieved by infusion of mu p75-SAP (0.4 µg/µl). Rabbit IgG-SAP (0.4 µg/µl) was used as control.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415

Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).

Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.

Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.

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

Ardini M, Vago R, Fabbrini MS, Ippoliti R (2022) From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?. Toxins (Basel) 14(9):579. doi: 10.3390/toxins14090579 PMID: 36136517

Objective: To give an overview describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.

Summary: “Suicide gene” therapy (SGT), consists of the selective delivery of genes coding for toxic proteins, into target cancer cells. This new and promising approach may overcome some of the issues related to the use of chemical agents (chemotherapy) such as as specificity, high dosages with accompanying side effects, and chemoresistance induction.

Cleverdon REG, Braun JL, Geromella MS, Whitley KC, Marko DM, Hamstra SI, Roy BD, MacPherson REK, Fajardo VA (2022) Sarco(endo)plasmic reticulum Ca2+-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx mice. iScience 25(9):104972. doi: 10.1016/j.isci.2022.104972 PMID: 36093052

Objective: To investigate whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice.

Summary: The study demonstrates that SERCA function is drastically impaired in young D2 mdx mice.

Usage: Western blot

Related Products: NO-L-Cysteine Mouse Monoclonal, Conjugated (Cat. #AB-T125)

Cao S, Wang Z, Xing L, Zhou L, Zhang W (2022) Bovine bone gelatin-derived peptides: Food processing characteristics and evaluation of antihypertensive and antihyperlipidemic activities. J Agric Food Chem 70(32):9877-9887. doi: 10.1021/acs.jafc.2c02982 PMID: 35917452

Objective: To evaluate the food processing properties of bovine bone gelatin-derived peptides (BGPs) and their effects and mechanisms on hypertension and hypertension complications in spontaneously hypertensive rats.

Summary: BGPs could alleviate hypertension and dyslipidemia in SHRs by inhibiting ACE/Ang II/AT1R and activating the Ang II/AT2R signaling pathway.

Usage: Angiotensin II receptor (AT-2R) Rabbit Polyclonal, affinity-purified

Related Products: Angiotensin II receptor (AT-2R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N28AP)

Goodyer WR, Beyersdorf BM, Duan L, van den Berg NS, Mantri S, Galdos FX, Puluca N, Buikema JW, Lee S, Salmi D, Robinson ER, Rogalla S, Cogan DP, Khosla C, Rosenthal EL, Wu SM (2022) In vivo visualization and molecular targeting of the cardiac conduction system. J Clin Invest e156955. doi: 10.1172/jci156955

Objective: To engineer targeted antibody conjugates directed against the cardiac conduction system (CCS) to allow visualization of the CCS in vivo.

Summary: Accidental injury to the CCS, a specialized set of cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. They generated a fully human monoclonal Fab (hCNTN2) that targets the CCS with high specificity.

Usage: Streptavidin-ZAP was reacted with biotinylated hCNTN2 Fab to create hCNTN2-SAP. 100 ug of either hCNTN2-SAP and control-SAP were injected into wild-type mice with a single tail-vein injection and hearts were harvested after 2 days.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372

Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.

Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).

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

Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem doi: 10.1111/jnc.15683

Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.

Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.

Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.

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

Eccardt AM, Pelzel RJ, Bell TP, Fisher JS (2022) Stimulation of Akt phosphorylation and glucose transport by metalloporphyrins with peroxynitrite decomposition catalytic activity. Catalysts 12(8):849. doi: 10.3390/catal12080849 PMID: 0

Objective: To determine whether a catalytic action of iron porphyrin compounds would be related to their stimulation of insulin signaling and glucose uptake in C2C12 myotubes.

Summary: Findings suggest that iron porphyrin compounds with both peroxynitrite decomposition activity and peroxidase activity can stimulate insulin signaling and glucose transport in skeletal muscle cells.

Usage: Western blot

Related Products: NO-L-Cysteine Mouse Monoclonal, Conjugated (Cat. #AB-T125)

Negueruela S, Morenilla C, Herrera M, Coca Y, Florez-Paz D, López-Cascales MT, Gomis A, Herrera E (2022) Perinatal correlated retinal activity is required for the wiring of visual axons in non-image forming nuclei. bioRxiv 2022.07.27.501692. doi: 10.1101/2022.07.27.501692

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)