Breathing is automatically adjusted by the brain based on the body’s carbon dioxide (CO₂) levels. Problems with the brain’s CO₂-sensing system can lead to dangerous hypoventilation disorders that are difficult to treat. Progesterone and its metabolite etonogestrel (ETO) are known to stimulate breathing and may improve the body’s response to elevated CO₂.
Researchers tested whether ETO could restore CO₂ sensing in rats after damaging key CO₂-sensitive neurons in the brainstem using SSP-SAP. In both male and female rats, greater loss of these neurons caused greater impairment of the CO₂ chemoreflex.
Now, ETO treatment improved breathing responses in female rats, especially when the damage was moderate. The recovery in females was linked to increased expression of two pH-sensing genes (Gpr4 and Task2) in the brainstem.
Interestingly, male rats did not show the same improvement, suggesting that ETO restores CO₂ sensing through a sex-specific mechanism.
These findings may help explain why progesterone-related therapies have shown mixed results and could guide future treatments for breathing disorders.
Developing reliable animal models can be time-consuming, complex, and difficult to control. Our saporin-based approach enables targeted elimination of specific cell populations, allowing you to create precise animal models for studying disease, behavior, and biological function—without the long timelines of traditional methods.
This approach has been widely used to generate models for neurological and disease-specific research, where selective removal of defined cell types is critical to understanding function and pathology.
Their study examined whether selective loss of inhibitory interneurons in the hippocampus was enough to trigger temporal lobe epilepsy with hippocampal sclerosis (TLE-HS+). Injection of stable substance P-saporin (SSP-SAP) into the hippocampus of rats, rapidly targeted and eliminated specific inhibitory neurons.
Within 4–6 days, the animals developed spontaneous seizures. Although these early seizures subsided, the frequency and duration of self-generated epileptiform events steadily increased over the following three months, demonstrating progressive epileptogenesis. The researchers also observed ongoing loss of hippocampal neurons (particularly in the CA1 and CA3 regions) and increasing astrogliosis, both hallmark features of hippocampal sclerosis seen in human TLE patients.
Overall, the findings show that selective disruption of hippocampal inhibitory circuitry is sufficient to initiate epilepsy and drive the development of pathological changes that closely resemble human temporal lobe epilepsy with hippocampal sclerosis.
Unlike other models of epilepsy, the SSP-SAP model (Cat. #IT-11) has very specific toxicity that does not cause early death in the animal. The animal will have a normal lifespan, continuing to experience seizures.
With our Animal Models, you can:
Selectively remove defined cell types in vivo
Model disease pathways and functional outcomes
Study behavioral and physiological changes
Accelerate research timelines with rapid model generation
Most models are ready in just 2 weeks, helping you move from hypothesis to data faster.
Memory loss is a common part of aging, but it varies greatly from person to person. Research shows that changes in the gut microbiome may play an important role in age-related cognitive decline. Certain gut bacteria, especially P. goldsteinii, increase with age and produce medium-chain fatty acids (MCFAs).
These bacterial products trigger inflammation in peripheral immune cells through a receptor called GPR84. The resulting inflammation disrupts signaling through the vagus nerve, reducing communication between the gut and the brain. Weakened gut–brain communication leads to reduced activity in the hippocampus, making it harder to form and store new memories.
The authors injected CCK–SAP and Blank-SAP (125 ng in 0.5 μl per ganglion) into the nodose ganglion of the vagus nerve to determine their role in cognitive decline.
The authors work suggests that in aged mice, memory could be improved by reducing P. goldsteinii, blocking GPR84 signaling, or restoring vagus nerve activity, suggesting new potential treatments for age-related memory loss.
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.
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).
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.
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.
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
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.
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
