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).
Lauer LT, Decarie-Spain L, Hayes AMR, Suarez AN, Bashaw A, Klug ME, Kao AE, Cheng R, Rea JJ, Subramanian KS, Nourbash A, Donohue KN, Schier LA, Myers K, Kanoski SE (2025) The vagus nerve promotes memory via septo-hippocampal acetylcholine: Implications for obesity-induced cognitive dysfunction. bioRxiv 2025.06.11.659206.
Objective: To demonstrate that nutrient consumption promotes hippocampal-dependent memory function via vagus nerve-mediated acetylcholine (ACh) release in the dorsal hippocampus (HPCd) from medial septum (MS) neurons.
Summary: Results identify a neurobiological mechanism whereby nutrient consumption promotes memory function, and reveals that disruption of this vagal-brain signaling system mediates Western Diet-associated memory impairments.
Usage: The antineuronal immunotoxin 192-IgG-SAP, which has been validated as an agent that selectively ablates neurons that produce acetylcholine was injected in the medial septum; 200nL (0.16mg/mL) were infused in three different coordinates that span the medial septum.
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.
Konturek-Ciesla A, Zhang Q, Kharazi S, Bryder D (2025) A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Nat Commun 16(1):5129. doi: 10.1038/s41467-025-60464-3 PMID: 40456713
Objective: Application of Hematopoietic stem cell (HSC) transplantation leads to treatment toxicity. Therefore, authors employed a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated HSC depletion to improve hematopoietic output and ameliorate age-compromised lymphopoiesis.
Summary: Authors demonstrate that young HSCs, once effectively engrafted in aged hosts, improve hematopoietic output and ameliorate age-compromised lymphopoiesis. This culminated in a strategy that robustly mitigates disease progression in a genetic model of myelodysplastic syndrome. These results suggest that non-genotoxic HSC transplantation could fundamentally change the clinical management of age-associated hematological disorders, offering a prophylactic tool to delay or even prevent their onset in elderly patients.
Usage: CD45-SAP (3 mg/kg) was administered to young (2 months) and aged (16 months) C57BL/6-CD45.2 mice
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) or Blank-SAP (IT-21) 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.
Oti GO, Basak A, Eason G, Kington S, Drago C, Smith L, Osman K, Smith CL, Keilholz A, Lever TE, Nichols NL (2025) Therapeutic potential of tongue exercise on tongue force/strength during swallowing in a rodent model of hypoglossal (xii) motor neuron loss. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.1188
Objective: To develop a rodent model of XII axis dysfunction by administering CTB-SAP to explore potential treatment for neuromuscular disorders.
Summary: The data demonstrate that the number of evoked swallows did not differ between groups, and threshold stimulation elicited fewer swallows compared to suprathreshold intensities.
Usage: Adult male rats were intralingually injected with either 25 ug CTB-SAP (IT-14) or control (CTB unconjugated to SAP)
