References

Okalova J, Alexander JS, Patel SR, Branella GM, Barichello de Quevedo C, Baldwin WH, Prince C, Chandrakasan S, Brown HC, Doering CB, Spencer HT (2026) Antimetabolites synergize with antibody drug conjugate-based non-genotoxic conditioning facilitating hematopoietic stem cell-directed lentiviral gene therapy. Mol Ther Adv doi: 10.1016/j.omta.2026.201780

Objective: To investigate the hypothesis that anti-CD117-sap is not effective as a single non-genotoxic conditioning agent in hematopoietic stem and progenitor cells (HSPCs)-directed lentiviral vector gene therapy for hemophilia A due to a lack of deep HSPC depletion in the bone marrow (BM).

Summary: The authors demonstrated how conditioning with non-genotoxic conditioning ADCs, such as Anti-CD117-SAP, causes cycling of residual HSPCs in the BM niche. There is potential of repurposing antimetabolites into these non-genotoxic conditioning regimens when combined with immune suppression to further target ADC-induced cycling HSPCs and augment depletion in the BM prior to HSCT.

Usage: A conjugate with Streptavidin-Saporin and biotinylated CD117 was developed. Mice were conditioned with the conjugate at doses ranging from 0.5 to 1 mg/kg.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

Tierno Lauer 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, Décarie-Spain L, Kanoski SE (2026) The vagus nerve promotes memory in rats via nutrient-induced septo-hippocampal acetylcholine signaling. Nat Commun doi: 10.1038/s41467-026-73896-2 PMID: 42236727

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: Recent findings highlight a role for vagus nerve-mediated gut-brain signaling in regulating higher-order cognitive processes. MS cholinergic neuron ablation, subdiaphragmatic vagotomy, and Western Diet impaired memory for meal location, suggesting that this signaling pathway functions to promote memories for eating events. Collectively, results identify a neurobiological mechanism whereby nutrient consumption enhances memory function and suggest that disruption of this vagal-brain signaling system mediates WD-associated memory impairments.

Usage: Rats were injected with either a 192-IgG-SAP (IT-01) in the MS (to ablate MS cholinergic neurons) or a control saporin (PR-01).

Related Products: 192-IgG-SAP (Cat. #IT-01), Saporin (Cat. #PR-01)

Gupta S, Kesler MT, Scantlebury MH, Sloviter RS, Teskey GC (2026) Modeling temporal lobe epilepsy with hippocampal sclerosis in rats using the selective neurotoxin stable substance P-saporin. Epilepsia doi: 10.1002/epi.70322 PMID: 42220243

Objective: To determine the time course of SSP-­SAP-­induced epileptogenesis, as well as the loss of principal cells and astrogliosis, two defining features of Temporal lobe epilepsy with hippocampal sclerosis (TLE-­ HS+)

Summary: Temporal lobe epilepsy with hippocampal sclerosis (TLE-­ HS+) is a common and often refractory form of human epilepsy. SSP-­SAP was internalized within 2 h after injection and was immunocytochemically undetectable by 5 days. Rats exhibited spontaneous electrographic and behavioral reactive seizures between days 4 and 6 after SSP-­SAP injection, with most seizures having a Racine score of either 1 or 2. This study confirms that the SSP-­ SAP model reproduces the defining features of human TLE and that a primary, selective, and longitudinally extensive γ- aminobutyric acidergic defect is sufficient to trigger epileptogenesis that results in TLE-­HS+.

Usage: 150 nL of SSP-SAP (0.04 ng/nL, IT-11) was injected at a rate of 1 nL/s into four unilateral sites along the longitudinal axis of the rat dentate gyrus. To determine the time course for SSP-­ SAP internalization (n=4), rats were perfused at 2 h and 1, 3, and 5 days following SSP-­ SAP administration. Following coronal cryosectioning of the hippocampus, sections were placed in a 500-­μL solution of 1:350 Saporin Goat Polyclonal, affinity-purified Alexa 488 (AB-15AP-FLA) and .01 mol·L−1 PBS at room temperature overnight. Sections were inspected and imaged at 40× with 4× digital zoom using an Olympus Fluoview FV3000 confocal microscope.

Related Products: SSP-SAP (Cat. #IT-11), Saporin Goat Polyclonal, affinity-purified Alexa488-labeled (Cat. #AB-15AP-FLA)

Zhang YW, Jia WX, Wang YQ, Zhou P, Zhang XY, Liu CW, Wang J, Lu XF, Dai CF (2026) Cerebrospinal fluid-contacting nucleus mediates the balance of depth during general anesthesia in mice. Neuropharmacology 111037. doi: 10.1016/j.neuropharm.2026.111037 PMID: 42214455

Objective: To investigate the role of the cerebrospinal fluid-contacting nucleus (CSF-CN), which directly interfaces with the CSF, in modulating general anesthesia in mice

Summary: The authors found that the CSF-CN plays a critical homeostatic role in general anesthesia. During deep anesthesia, it may buffer excessive anesthetic inhibition, whereas during emergence, it regulates the recovery process to prevent premature or overly rapid awakening.

Usage: CSF-CN was labeled by administering the retrograde tracer cholera toxin subunit B-594 into the lateral ventricle, and it was selectively ablated using a conjugate of saporin and cholera toxin subunit B.

Related Products: CTB-SAP (Cat. #IT-14)

Gerasimov KA, Ignasheva YE, Dobryakova YV, Korotkova TA, Koryagina AA, Markevich VA, Bolshakov AP (2026) Overexpression of WNT3a in the hippocampus can partly alleviate deficits in animal models of Alzheimer’s Disease. Neurochem Res 51(3):174. doi: 10.1007/s11064-026-04793-9 PMID: 42185674

Objective: To investigate whether enhancing WNT signaling through hippocampal overexpression of the WNT3a ligand can mitigate functional deficits in two distinct animal models of Alzheimer’s disease (AD) pathology.

Summary: The authors used a rat model of cholinergic deficit, induced by intraseptal 192-IgG-SAP injections, and a transgenic 5XFAD mouse model of amyloidosis. Findings demonstrate that targeted WNT3a overexpression in the hippocampus can partially alleviate synaptic and functional deficits in AD models by directly modulating synaptic plasticity, primarily through the restoration of the Wnt/β-catenin pathway.

Usage: Rat model with intraseptal 192-IgG-SAP (IT-01) injections

Related Products: 192-IgG-SAP (Cat. #IT-01)

Voisin T, Gheziel N, El Samrout C, Martin J, Bradaia A, Iftinca M, Defaye M, Charron A, Abdullah NS, Changenot C, Gonzalez AA, Depluech A, Labit E, Saint-Laurent N, Staurengo-Ferrari L, Erdogan O, Tauber M, Loste A, Serhan N, Villa-Hernandez S, Chiu IM, Moqrich A, Altier C, Basso L, Gaudenzio N (2026) Skin inflammation and itch response are independently regulated by distinct nociceptor subsets. Immunity 59(5):1237-1252.e9. doi: 10.1016/j.immuni.2026.03.020 PMID: 41990747

Objective: To show the presence of two distinct and adaptive neuronal circuits that independently regulate allergic inflammation and itch in the skin in a model of allergic contact dermatitis (ACD).

Summary: To confirm the role of NP1 neurons in CHS-associated itch, the authors targeted IB4+ NP1 neurons using saporin-conjugated IB4. Neuronal loss was confirmed, as well as a partial depletion of IB4+ neurons and GFRα2+ neurons, but not TH+ neurons, in IB4-sap mice. Chemical depletion of IB4+ neurons led to a significant decrease in the number of ATF3+ neurons, little or no differences in immune response or pathology, but a significant reduction in scratching behavior.

Usage: Intrathecal injections were performed and mice received 5 μL of either IB4-saporin (IB4-SAP, 1.5μg/mouse; IT-10) or control saporin (650ng/mouse; PR-01) diluted in sterile PBS.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Miller J, Keilholz A, Smith C, Lever T, Nichols N (2026) Impact of tongue exercise on hypoglossal nucleus TrkB expression in a rodent model of hypoglossal motor neuron degeneration. American Physiology Summit 41(S1) doi: 10.1152/physiol.2026.41.S1.2300331

Objective: To investigate treatments to improve upper airway function primarily due to loss of hypoglossal lower motor neurons (XII LMNs) in individuals with neurodegenerative diseases.

Summary: Preliminary data suggest XII TrkB expression in CTB-SAP + tongue exercise rats is similar to control rats but is increased vs. CTB-SAP + sham exercise rats, providing evidence of the BDNF pathway underlying tongue exercise-induced changes following XII LMN loss. These results would suggest that the BDNF pathway could be a target for treatment for upper airway deficits in individuals with neurodegenerative diseases.

Usage: Intralingual injection of CTB-SAP (IT-14) in rat

Related Products: CTB-SAP (Cat. #IT-14)

Burd E, Keilholz A, Attari M, Smith C, Bunyak F, Lever T, Nichols N (2026) Impact of targeted tongue exercise on genioglossus sarcomere and mitochondria morphology in a rodent model of hypoglossal motor neuron death. American Physiology Summit 41(S1) doi: 10.1152/physiol.2026.41.S1.2301276

Objective: To establish a rodent model for studying the impact of XII LMN degeneration and developing therapies to improve swallowing and breathing function/coordination.

Summary: Studies have shown significant degenerative changes in genioglossus sarcomere and mitochondria morphology in rats with induced XII LMN death; however, the impact of tongue exercise on these morphological changes remains unknown. The authors established a rodent model using intralingual injections of CTB-SAP and studied ultrastructural changes in genioglossus sarcomere and mitochondria morphology using transmission electron microscopy and computational analysis. Preliminary data suggests that CTB-SAP + exercise rats demonstrate mitigation of degenerative mitochondrial morphology compared to CTB-SAP + sham exercise rats.

Usage: intralingual injection in adult male rats with CTB-SAP (IT-14) or control (CTB unconjugated to SAP) and subjected them to either sham or tongue exercise

Related Products: CTB-SAP (Cat. #IT-14)

Keilholz A, Ahmadzadeh E, Cornelius-Green J, Osman K, Smith C, Cummings K, Lever T, Nichols N (2026) Modulation of orexinergic neurons in the perifornical region of the hypothalamus impacts tongue motility and hypoglossal motor output in an inducible rodent model of hypoglossal motor neuron degeneration. American Physiology Summit 41(S1) doi: 10.1152/physiol.2026.41.S1.2300706

Objective: To examine role of orexinergic neurons in the perifornical region of the hypothalamus (PeF) project to the XII nucleus in treatment for patients with motor neuron diseases such as amyotrophic lateral sclerosis (ALS).

Summary: Aerobic and limb-based exercise has been shown to increase brain derived neurotrophic factor (BDNF) and orexinergic (OX) expression, which improved functional outcomes in ALS patients and rodent models. Results suggest that perifornical region of the hypothalamus (PeF) OX neurons promote XII plasticity to improve XII axis function following XII LMN loss.

Usage: Rodent model using intralingual injection in adult male rats with CTB-SAP (IT-14)

Related Products: CTB-SAP (Cat. #IT-14)

Keilholz AN, Lopez S, Attari M, Nguyen NP, Henry J, Smith CL, Feldberg A, Osman KL, Golzy M, Bunyak F, Lever TE, Nichols NL (2026) Impact of tongue exercise on hypoglossal axis survival, structure, and output in a rodent model of hypoglossal motor neuron degeneration. J Neurophysiol doi: 10.1152/jn.00631.2024 PMID: 42012472

Objective: To investigate the effects of a high-repetition/low-resistance tongue exercise paradigm on XII axis survival, structure, and output in adult male Sprague Dawley rats.

Summary: Intralingual injections of CTB-SAP result in decreased XII motor neuron survival and degenerative changes in the XII nerve consistent with what is seen in many motor neuron diseases. While these deficits are not mitigated by tongue exercise, the authors observed increased microglial fractional area/density in the XII nucleus of CTB-SAP + exercise rats.

Usage: Rats received intralingual injection of either CTB-SAP (IT-14) or unconjugated CTB + SAP (PR-01).

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)