Pandala N, De Melo Haefeli L, Lang M, Stone EM, Mullins RF, Tucker BA, Han IC (2025) Development of a targeted choroidal injury model for the study of retinal degenerations and therapeutic cell replacement. bioRxiv 2025.07.29.667466. doi: 10.1101/2025.07.29.667466
Summary: The choroid is a vascular structure that provides nutrients to the photoreceptors by diffusion as well as removal of waste from the outer retina, essentially enabling proper retinal function. Loss of the choroid is a crucial pathophysiologic step in a wide range of retinal diseases. However a current limitation in developing choroidal cell replacement is the lack of a reliable injury model to allow study of transplantation strategies. Existing models rely on either ablative injury to the choroid with laser photocoagulation, but can damage unintended structures, or systemic sodium iodate administration, which causes diffuse, progressive choroidal injury. Authors were able to show suprachoroidal injection of anti-CD38 and anti-CD105 saporin conjugates resulted in targeted, localized, and non-progressive choroidal injury in rats. Immunotoxin-based models of targeted choroidal injury may be useful for understanding pathways of retinal degeneration and facilitating development of therapies for diseases involving choroidal cell loss.
Lee H, Hor CC, Horwitz LR, Xiong A, Su XY, Soden DR, Yang S, Cai W, Zhang W, Li C, Radcliff C, Dinh A, Fung TLR, Rovcanin I, Pipe KP, Xu XZS, Duan B (2025) A dedicated skin-to-brain circuit for cool sensation in mice. Nat Commun 16(1):6731. doi: 10.1038/s41467-025-61562-y PMID: 40721582
Objective: To investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
Summary: The study identifies Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation reveal distinct sensory processing roles for various neuronal subtypes.
Usage: Bombesin-SAP (IT-40), or control conjugate Blank-SAP (IT-21), was administered intrathecally at a dose of 400 ng in 10 μL sterile saline to ablate GRPR+ spinal neurons and assess their role in sensory behavior.
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.
Noble EE, Harris RBS (2025) Leptin in the VMH contributes to the initial overconsumption of palatable diets by rats. Am J Physiol Endocrinol Metab 329(1):E1-E17. doi: 10.1152/ajpendo.00090.2025 PMID: 40418155
Objective: To determine whether leptin receptor–expressing neurons in the ventromedial hypothalamus (VMH) contribute to the initial overconsumption of a high-fat diet in rats.
Summary: Ablation of VMH leptin receptor–expressing neurons using Leptin-SAP prevented the early hyperphagic response to a high-fat diet in male rats but had no long-term impact on energy intake, body weight, or glucose clearance. These findings suggest VMH leptin signaling plays a key role in initiating, but not maintaining, diet-induced hyperphagia.
Usage: Leptin-SAP (IT-47) was stereotaxically injected into the VMH of male and female rats (20 ng in 80 nL) to ablate leptin receptor–expressing neurons. This targeted lesion confirmed the role of VMH leptin signaling in mediating early-phase overeating in response to a high-fat diet.
Szysiak N, Kosior-Korzecka U, longo V, Patkowski K, Greguła-Kania M, Nowakiewicz A, Bochniarz M,Junkuszew A (2025) Influence of neurokinin b, dynorphin a and kisspeptin-10 on in vitro gonadotropin secretion by anterior pituitary cells isolated from pubescent ewes. J Vet Res doi: 10.2478/jvetres-2025-0003
Objective: The aim of the study was to analyze the direct effect of the hypothalamic neuropeptides kisspeptin-10, neurokinin B, and dynorphin A on gonadotropin secretion by pituitary cells isolated from pubescent ewes.
Summary: Puberty is a multifactorial and complex process in animal development and in the case of livestock, timely attainment of sexual maturity contributes to increased reproductive efficiency, which leads to higher profitability. Studies revealed that kisspeptin, neurokinin B and dynorphin neuropeptides, collectively referred to as KNDy neuropeptides, are recognized as the key neuropeptides produced and secreted by the arcuate nucleus of the hypothalamus (ARC), and involved in the endocrine regulation of the onset of puberty. They all play roles in the endocrine regulation of the hypothalamic-pituitary-ovarian (HPO) axis in puberty. Kisspeptin-10, NKB and Dyn A had a direct impact on gonadotropin secretion by ovine pituitary cells. However, a detailed explanation of their role in gonadotropin secretion by the anterior pituitary gland in sheep and their impact on the regulation of the HPO axis during sexual maturation or in the pathomechanism of delayed puberty requires further studies.
Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.
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.
Anderson KL (2025) Neural mechanisms of context-sensitive behavior in the adult male zebra finch. City Univ NY Thesis.
Objective: To test whether oxytocin and dopamine mediate the influence of the social behavior network on the vocal control network in songbirds, enabling context-dependent changes to song.
Summary: The study reveals direct anatomical links between hypothalamic nodes of the social behavior network and the vocal control network. Blocking oxytocin receptors disrupts appropriate female-directed song and correlated network activity.
Usage: To assess brain access and persistence of intranasal compounds, Oxytocin-SAP (IT-46) was delivered intranasally at 1 μg/ml (12 μL total, 0.0012 mg per bird).
Chauhan P, Hu S, Sheng WS, Prasad S, Lokensgard JR (2025) bTRM control of murine cytomegalovirus cns reactivation. 26(11):5275. doi: 10.3390/ijms26115275 PMID: 40508083
Objective: To determine the role of CD8+ and CD103+ brain-resident memory T cells (bTRMs) in controlling murine cytomegalovirus (MCMV) reactivation in the central nervous system.
Summary: Depleting CD103+ bTRMs led to transient viral gene expression and delayed recovery of infectious virus from explants, implicating these cells in maintaining latency. bTRM depletion also triggered expression of disease-associated microglial genes, suggesting a role in modulating neuroimmune responses.
Usage: Anti-CD103-SAP (IT-50) was injected intracerebroventricularly (2 µg) to selectively deplete CD103+ bTRMs in latently infected mice. This targeted depletion achieved ~90% T-cell reduction and was critical for assessing viral reactivation and microglial activation phenotypes.
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.
Kozlova E, Lam A, Alam S, Shum J, Denys M, Berdasco C, de-Lartigue G, Curras-Collazo M (2025) Do CCKA receptor containing vagal afferent neurons mediate gut-brain inflammatory signals?. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.2035
Objective: To investigate whether CCKA receptor, containing vagal afferent neurons (VANs), mediate gut-brain inflammatory signaling and contribute to the systemic immune response following an LPS challenge.
Summary: This abstract reports that ablation of CCKAR+ VANs via CCK-SAP reduced LPS-induced IL-6 levels and brain c-Fos expression, indicating a blunted inflammatory response. These findings support the role of CCKAR+ VANs in gut-brain immune signaling and their potential as therapeutic targets.
Usage: CCK-SAP (IT-31) was bilaterally injected into the nodose ganglia (250 nL, 250 ng/μL) to ablate CCKA receptor–expressing vagal afferents.
