Nazmuddin M, Stammes MA, Klink PC, Vernes MK, Bakker J, Langermans JAM, van Laar T, Philippens IHCHM (2025) Stereotactic lesioning of cholinergic cells by injection of ME20.4 Saporin in the nucleus basalis of Meynert in a rhesus monkey (Macaca mulatta). J Neuropathol Exp Neurol nlaf081. doi: 10.1093/jnen/nlaf081 PMID: 40673943
Objective: To describe a procedure to inject ME20.4-SAP, an immunotoxin that specifically binds to and depletes cholinergic neurons stereotactically into the nucleus basalis of Meynert (NBM) of a rhesus monkey (Macaca mulatta).
Summary: A digital non-human primate brain atlas was co-registered to the brain of the monkey. A custom-designed cranial chamber was also implanted to the skull to guide the injection. The effects of the ME20.4-SAP injections were evaluated in vivo with PET-CT using [18F]-FEOBV as a radiotracer. This approach yielded reliable spatial accuracy and successful delivery of ME20.4-SAP into the NBM. This saporin-mediated selective destruction of cholinergic neurons in the NBM, using MRI-guidance and a cranial chamber, offers a promising method to study the pathophysiology of NBM degeneration and possible therapeutic interventions.
Usage: The first dose was chosen based on previous NBM lesioning works in common marmosets where infusing 1.4 μg ME20.4-SAP (Cat. #IT-15, in a concentration of 0.20 μg/μl) into each side of the NBM produced partial NBM depletion. At the second injection session, 5 μg ME20.4-SAP (in 0.5 μg/μl solution) was administered into each NBM side.
Ren X, Wang Y, Zhang Y (2025) Targeted depletion of dysfunctional hematopoietic stem cells mitigates myeloid-biased differentiation in aged mice. Cell Discov 11:56. doi: 10.1038/s41421-025-00810-3 PMID: 40490480
Objective: To develop and evaluate a targeted strategy for depleting dysfunctional, myeloid-biased CD150-high hematopoietic stem cells (HSCs) in aged mice to restore balanced hematopoiesis and mitigate aging-related blood disorders.
Summary: The study used an antibody-toxin conjugate to selectively eliminate CD150-high HSCs, improving lymphoid-to-myeloid ratios, reducing platelet hyperproduction, and restoring hematopoietic balance in aged mice. Treatment preserved functional CD150-low HSCs and showed minimal off-target or systemic toxicity.
Usage: Streptavidin-ZAP (IT-27) was combined with a biotinylated anti-CD150 antibody to generate Anti-CD150-SAP (IT-103). This conjugate was used at doses of 1–2 mg/kg in vivo and as low as 0.01 nM in vitro to specifically deplete CD150-high HSCs while sparing CD150-low populations.
Roberts AG, Meyer L, Norton M, Phuah P, Alonso AM, Dowsett GKC, Cheng S, Dunsterville C, Liu J, Chung PE, Tao Y, Smitherman-Cairns T, Deutsch AB, Chatterjee A, Lam BYH, Hanyaloglu AC, JOnes B, Yeo GSH, Salem V, Murphy KG (2025) Enteropancreatic neurons drive the glucoregulatory response to ingested lipid. bioRxiv 2025.05.09.652620. doi: 10.1101/2025.05.09.652620
Objective: To determine whether NTSR1-expressing enteropancreatic neurons mediate the glucose-lowering effects of dietary olive oil and neurotensin, and to characterize their physiological role in glucose homeostasis.
Summary: The study demonstrates that neurotensin improves glucose tolerance by activating NTSR1-expressing enteropancreatic neurons, which connect the gut and pancreas. Ablation or disruption of these neurons abolished the glucoregulatory effects of both neurotensin and olive oil, establishing their necessity and sufficiency in this pathway.
Usage: Neurotensin-SAP (IT-56) was unilaterally injected into the nodose ganglia (0.5 μL at 1.5 μg/μL) to ablate NTSR1-expressing vagal neurons. This targeted lesioning helped confirm that peripheral vagal neurons were not responsible for mediating the glucose-lowering effects of neurotensin.
