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)
Burd E, Attari M, Smith C, Bunyak F, Lever, T, Nichols N (2025) Genioglossus sarcomere and mitochondria morphology in a rodent model of hypoglossal motor neuron death. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.0879
Objective: To develop a novel rodent model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to induce targeted loss of XII LMNs and XII motor output
Summary: Authors hypothesized that XII LMN loss leads to degenerative changes in genioglossus sarcomere and mitochondria morphology in CTB-SAP rats. Ultrastructural changes in genioglossus sarcomere and mitochondria morphology were studied. The preliminary data suggests a dysregulation of sarcomere ultrastructure, particularly Z-lines, and a significant increase in mitochondrial perimeter and maximum Feret’s diameter in CTB-SAP rats vs. controls, consistent with degenerative changes and a potential in flammatory response in genioglossus muscle cells following the loss of XII LMNs.
Usage: Intralingual injection of adult male rats with CTB-SAP (IT-14)
Lewis R, Smith C, Burd E, Nichols N (2025) Phrenic motor nucleus astrocytic density and morphology in a rodent model of respiratory motor neuron death. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.1115
Objective: Authors hypothesized that astrocytic density would be increased and astrocytic morphology would be altered in the phrenic motor nucleus over the course of motor neuron death in CTB-SAP rats vs. controls.
Summary: The number of astrocytes was significantly increased in CTB-SAP-treated rats. Furthermore, an astrocytic morphological analysis revealed that CTB-SAP rats have significantly increased branch number, number of endpoints, filament volume, and number of intersections, as well as significantly decreased branch volume and branch length inside the phrenic motor nucleus. Additionally, astrocytic number in the non-phrenic motor nucleus region immediately outside of the phrenic motor nucleus was significantly increased while branch length was significantly decreased in CTB-SAP treated rats. Collectively, these findings are indicative of a reactive morphological state in the phrenic motor nucleus in CTB-SAP rats and suggest that astrocytes may also be an origin of TNF-α to impact phrenic plasticity and ultimately breathing.
Usage: Intrapleural injection of CTB-SAP (IT-14) in rat
Keilholz A, Henry J, Osman K, Smith C, Haxton C, Ozden I, Lever T, Nichols N (2025) Impact of TrkB receptor modulation on tongue exercise-induced plasticity in an inducible rodent model of hypoglossal (xii) motor neuron death. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.0788
Objective: Authors hypothesized that the source of tongue exercise-induced plasticity in CTB-SAP rats arises from a BDNF- dependent pathway to preserve upper airway function.
Summary: Authors targeted tropomyosin receptor kinase B (TrkB) by delivery of either a TrkB receptor antagonist (ANA-12) or vehicle (veh; 50:50 DMSO+aCSF) into the XII nucleus of the brainstem in adult male rats for the following groups: 1) control+sham exercise+veh 2) CTB-SAP+exercise+veh 3)CTB-SAP+exercise+ANA-12. The effect of TrkB receptor inhibition on tongue exercise-induced plasticity was assessed by conducting behavioral assays. The findings suggest that CTB-SAP+exercise+ANA-12 rats have decreased lick force/rate vs. CTB-SAP+/-exercise+/-veh rats as well as control +/-exercise+/-veh rats.
Usage: Intralingual injection of CTB-SAP (IT-14) in rat
