Windhorst U, Dibaj P (2025) Nociception and acute pain: Neurotransmitters and neuromodulators. Preprints.org preprints202508.0487.v1. doi: 10.20944/preprints202508.0487.v1
Objective: To review the huge variety of additional neurotransmitters, neuromodulators and hormones in the nociceptive and pain system
Summary: Nociception and acute pain are governed by a dynamic interplay of structures and substances, modulated by internal and external factors, and vulnerable to pathological reorganization.
Usage: The injection of anti‐DBH‐SAP induced neurodegeneration restricted to the NA A5 cell group and confirmed by the decrease in the number of NA neurons only in the A5 group.
Nie AA, Taylor BK (2025) The pharmacotherapeutic potential of neuropeptide Y for chronic pain. J Intern Med 298(4):280-896. doi: 10.1111/joim.20118 PMID: 40754889
Objective: To evaluate how neuropeptide Y (NPY) and its receptor subtypes (Y1 and Y2) regulate acute and chronic pain, and to explore the therapeutic potential of targeting these pathways for the treatment of neuropathic and inflammatory pain.
Summary: The review highlights that spinal Y1-interneurons contribute to both sensory and affective components of chronic pain and that Y1 receptor activation can inhibit pronociceptive signaling. Prior studies using NPY-SAP demonstrated that ablation of Y1-expressing neurons reduces hypersensitivity in models of nerve injury and inflammation, supporting Y1 modulation as a therapeutic avenue.
Usage: NPY-SAP (IT-28) was referenced in the context of earlier studies employing intrathecal administration to ablate spinal Y1-interneurons.
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 PMID: 40766580
Objective: To report a new targeted choroidal injury model using saporin conjugates and compare them to models of systemic sodium iodate administration.
Summary: Suprachoroidal administration of Anti-CD38-SAP or Anti-CD105-SAP resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose.
Usage: Anti-CD38-SAP (IT-96) or Anti-CD105-SAP (IT-80) were diluted in sterile PBS at a concentration of 0.05 μg/μl. To induce selective choroidal cell injury, 10μl of saporin conjugate solution was delivered via suprachoroidal injection.
We are highlighting one of our saporin conjugates, Bombesin-SAP. A tool for depleting cells that express gastrin releasing peptide receptor (GRPR). Bombesin is a 14-amino acid peptide actually found in frog skin. The human equivalent GRP has been detected in itch pathways and plays a role in eating behaviors.
Their objective was to investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
The authors were able to administer Bombesin-SAP (IT-40) or a control conjugate (Blank-SAP, IT-21) intrathecally to ablate GRPR-positive spinal neurons to assess their role in sensory behavior.
In their study, they identified Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation revealed distinct sensory processing roles for various neuronal subtypes.
Nazmuddin M, Stammes MA, Klink PC, Vernes MK, Bakker J, Langermans JAM, van Laar T, Philippens IHCHM (2026) 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 85(1):58-70. 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.
Nollet M, Ba W, Soto BA, Yin C, Lignos L, Jovic K, Vyssotski AL, Yustos R, Franks NP, Wisden W (2025) The selective amyloid-driven failure of cholinergic medial septal neurons in aging mice perturbs REM sleep, cognition and emotion, and broadcasts amyloid to other brain regions. bioRxiv 2025.07.09.663930. doi: 10.1101/2025.07.09.663930
Objective: To look genetically at the intersection of amyloid pathology and the cholinergic system in Alzheimer’s disease (AD).
Summary: The broadcasting of amyloid by medial septal cholinergic cells is a notable feature, and potentially important in human pathology, selective genetic lesioning of about one third of the medial septal cholinergic cells, independent of amyloid, gave the same REM sleep, cognitive and emotional phenotypes. Thus, it is the killing of the cholinergic cells by amyloid, and therefore the missing acetylcholine, and not the secreted/deposited amyloid in the hippocampus and other areas, that is the critical feature. These findings underscore the interest in revitalizing the classic cholinergic hypothesis of AD. Restricting pathological amyloid expression to MS cholinergic neurons, so that their health is compromised by amyloid, is sufficient to reproduce many AD-like symptoms, highlighting the critical role of these cells in early AD pathogenesis, REM sleep regulation, emotion and cognition.
Usage: Cholinergic neurons throughout the forebrain in mice were lesioned with mu p75-SAP. The loss of cholinergic innervation exacerbated neurovascular impairments and cerebral amyloid angiopathy progression in the cortex and hippocampus
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) or Blank-SAP (IT-21) 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.
Bai J, Cheng K, Zhang N, Chen Y, Ni J, Wang Z (2025) Research advances in dysphagia animal models. Animal Model Exp Med 8(9):1579-1589. doi: 10.1002/ame2.70054 PMID: 40566744
Objective: To summarize the establishment and evaluation of dysphagia animal models in stroke, Parkinson’s disease, and ALS, in three kinds of experimental animals, providing a basis for the selection of appropriate animal models of dysphagia.
Summary: There are very few studies of diseases such as stroke, PD, and ALS using other mammal and NHP dysphagia models. Moreover, there are substantial labor, cost, time, and ethics-related issues that limit the widespread use of these animal models in research. Nevertheless, large animal models serve as a crucial intermediary between rodent studies and clinical trials, significantly enhancing the translational potential of preclinical research findings.
Usage: Lori et al. used an ALS model created by intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) to induce apoptosis of sublingual motoneurons to study the effect of hypoglossal motor neuron death without many complications.
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 69(1):121-129. doi: 10.2478/jvetres-2025-0003 PMID: 40144066
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.
Orciani C, Foret MK, Cuello AC, Carmo SD (2025) Long-term nucleus basalis cholinergic lesions alter the structure of cortical vasculature, astrocytic density and microglial activity in Wistar rats. Neurobiology of Aging 150:132-145. doi: 10.1016/j.neurobiolaging.2025.03.006 PMID: 40121723
Objective: To investigate the effects of the Basal forebrain cholinergic neurons (BFCNs) input on neurovascular unit (NVU) components.
Summary: To address this issue, the authors immunolesioned the nucleus basalis by administering injections of the cholinergic immunotoxin 192-IgG-SAP. Authors observed a significant reduction in cortical vesicular acetylcholine transporter-immunoreactive synapses. This was accompanied by changes in the diameter of cortical capillaries and precapillary arterioles, as well as lower levels of vascular endothelial growth factor A (VEGF-A). Additionally, the cholinergic immunolesion increased the density of cortical astrocytes and microglia in the cortex. The loss of nucleus basalis cholinergic input negatively impacts cortical blood vessels, NVU components, and microglia phenotype.
Usage: 192-IgG-SAP (2.6 mg/ml, IT-01) was injected at 0.5 μg/μl (1.0 μl/ hemisphere).
