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Modeling temporal lobe epilepsy with hippocampal sclerosis in rats using the selective neurotoxin stable substance P-saporin
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)
Modelling Temporal Lobe Epilepsy with Sclerosis in the SSP-Saporin ‘Trojan Horse’ Model
Gupta S (2026) Modelling Temporal Lobe Epilepsy with Sclerosis in the SSP-Saporin ‘Trojan Horse’ Model. Univ Calgary Thesis.
Objective: To confirm that the SSP-SAP model reproduces the defining features of human TLE and that a primary and selective GABAergic defect is sufficient to trigger epileptogenesis that results in TLE-HS+.
Summary: The author hypothesized that intrahippocampal SSP-SAP administration will first cause rats to exhibit reactive behavioural seizures, followed by self-generated epileptiform activity that will develop into electrographic seizures. Rats will also develop TLE anatomically characterized by progressive principal cell loss and astrogliosis.
Usage: Rats were stereotaxically injected with 150 nL of SSP-SAP (IT-11, 0.04 ng/nL) at 4 sites in the hippocampus.
Related Products: SSP-SAP (Cat. #IT-11)
Investigating anxiety-like behaviors and basolateral amygdala dysfunction in a novel rat model of Parkinson’s disease
Lipari NR (2025) Investigating anxiety-like behaviors and basolateral amygdala dysfunction in a novel rat model of Parkinson’s disease. SUNY Binghamton Thesis.
Objective: To create a unique model of PD with improved face validity, and non-motor symptoms.
Summary: This work helped further characterize motor and non-motor symptoms while providing potential underlying physiological markers for early disease course in a unique animal model of Parkinson’s disease (PD).
Usage: It has been demonstrated that lesioning of the basolateral amygdala with the targeted toxin stable substance P (SSP) saporin, a toxin that selectively lesions neurons which express neurokinin1 receptors, increases anxiety-like behaviors in rats.
Related Products: SSP-SAP (Cat. #IT-11)
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The progestinic drug, etonogestrel, rescues breathing in a rodent model of central chemoreflex impairment
Janes T, Cardani S, Pagliardini S (2024) The progestinic drug, etonogestrel, rescues breathing in a rodent model of central chemoreflex impairment. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.978
Objective: Assessing the efficacy of etonogestrel as a treatment to congenital hypoventilation syndrome (CCHS).
Summary: Etonogestrel can stimulate breathing and CO2-chemoreflexes and could be used to treat congenital hypoventilation syndrome. A model of CCHS was created in rats through the ablation of retrotrapezoid nucleus neurons with substance-P saporin. In this CCHS model-rat Etonogestrel was assessed for its ability to return breathing back to normal and for its mechanism of action.
Usage: Rats were lesioned with SSP-SAP [IT-11] targeting the retrotrapezoid nucelus (R.V.N.) neurons.
Related Products: SSP-SAP (Cat. #IT-11)
Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?
Souza GMPR, Abbott SBG (2024) Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?. Respir Physiol Neurobiol 322:104217. doi: 10.1016/j.resp.2024.104217 PMID: 38237884
Objective: To discuss the current definition of chemoreceptor neurons in the retrotrapezoid nucleus (RTN) and describe how this definition has evolved over time.
Summary: Studies offer evidence that RTN neurons are indispensable for the central respiratory chemoreflex in mammals and exert a tonic drive to breathe at rest. Moreover, RTN has an interdependent relationship with oxygen sensing mechanisms for the maintenance of the neural drive to breathe and blood gas homeostasis. Collectively, RTN neurons are a genetically-defined group of putative central respiratory chemoreceptors that generate CO2-dependent drive that supports eupneic breathing and stimulates the hypercapnic ventilatory reflex.
Usage: One widely adopted approach to eliminate RTN neurons utilizes local microinjections of the ribosomal-toxin Saporin conjugated to the analogue of substance-P (SSP-SAP),which results in cell death of neurokinin receptor 1-expressing neurons in a concentration-dependent manner.
Related Products: SSP-SAP (Cat. #IT-11)
See Also:
- Nattie EE et al. Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603-616, 2002.
- Souza GMPR et al. Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats. J Physiol 596(13):2521-2545, 2018.
- Takakura AC et al. Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585, 2014.
- Takakura AC et al. Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apneic threshold in rats. J Physiol 586:2975-2991, 2008.
Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment
Janes TA, Cardani S, Saini JK, Pagliardini S (2024) Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) e14093. doi: 10.1111/apha.14093 PMID: 38258900
Objective: Examine the use of progestins and synthetic progestins in the stimulation of breathing, especially after chemoreflexive impairment.
Summary: Central CO2 chemoreflex is important for respiratory control. The retrotrapezoid nucleus is involved in CO2 chemosensitivity where its removal or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Progesterone stimulates restful breathing and CO2 chemoreflexes. The authors investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could help in the recovery of respiratory chemoreflexes following lesion of the retrotrapezoid nucleus via a SP-SAP.
Usage: Rats were injected with 26-43.3 ng/ul of SP-SAP (IT-11) or 46.7 ng/ul of Blank-SAP (IT-21), with 150 nl per injection.
Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)
Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice
Maiarù M, Leese C, Silva-Hucha S, Fontana-Giusti S, Tait L, Tamagnini F, Davletov B, Hunt SP (2024) Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice. J Pain 25(6):104466. doi: 10.1016/j.jpain.2024.01.331 PMID: 38218509
Summary: The authors discuss how Substance P-Botulinum is used to try to replicate the permanent results achieved with Substance P-Saporin (SP-SAP, SSP-SAP).
Related Products: SSP-SAP (Cat. #IT-11)
See Also:
- Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
- Nichols ML et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558-1561, 1999.
- Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
- Wiley RG et al. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345, 2007.
- Vierck CJ et al. Comparison of operant escape and innate reflex responses to nociceptive skin temperatures produced by heat and cold stimulation of rats. Behav Neurosci. 2004;118(3):627-35.
Neuromedin B-expressing neurons in the retrotrapezoid nucleus regulate respiratory homeostasis and promote stable breathing in adult mice
Souza GMPR, Stornetta DS, Shi Y, Lim E, Berry FE, Bayliss DA, Abbott SBG (2023) Neuromedin B-expressing neurons in the retrotrapezoid nucleus regulate respiratory homeostasis and promote stable breathing in adult mice. J Neurosci JN-RM-0386-23. doi: 10.1523/JNEUROSCI.0386-23.2023 PMID: 37290937
Objective: To develop a transgenic mouse model and demonstrate that retrotrapezoid nucleus (RTN) neurons are fundamental for respiratory homeostasis and mediate the stimulatory effects of CO2 on breathing.
Summary: This study uses a transgenic Nmb-Cre mouse model to demonstrate that RTNNmb neurons are crucial for CO2-dependent breathing in mice. It provides evidence that these neurons play a key role in respiratory homeostasis and might be linked to sleep-disordered breathing in humans. Cre-dependent cell ablation and optogenetics show RTNNmb neurons’ essential function in mediating the hypercapnic ventilatory response, highlighting the importance of these neurons in maintaining eupneic breathing.
Usage: This publication references the use of SSP-SAP (IT-11) to target RTN neurons.
Related Products: SSP-SAP (Cat. #IT-11)
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Identification of an essential spinoparabrachial pathway for mechanical itch
Ren X, Liu S, Virlogeux A, Kang SJ, Brusch J, Liu Y, Dymecki SM, Han S, Goulding M, Acton D (2023) Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 30:S0896-6273. doi: 10.1016/j.neuron.2023.03.013 PMID: 37023756
Objective: Study pathways of mechanical and chemical itch.
Summary: Mechanical and chemical itch are controlled by separate pathways within the body. Gpr83ligand PEN peptide conjugated to saporin (PEN-SAP) was used to selectively ablate CAlcrl projection neurons, alleviating mechanical itch sensitivity in wild-type mice. Substance-P saporin (SSP-SAP) was injected into mice and used as a negative control for the ablation of itch-sensitive neurons in the areas targeted. The ablated mice maintained mechanical itch sensitivity.
Usage: Intrathecal injections of SSP-SAP (IT-11; 100 ng/10 ml 0.9% sterile saline), biotinylated Gpr83 ligand (PEN) conjugated to Strepavidin-ZAP (IT-27), PEN-SAP, 3 ug/10 ml, 0.9% sterile saline, or control Blank-SAP (IT-21) in mice.
Related Products: SSP-SAP (Cat. #IT-11), Streptavidin-ZAP (Cat. #IT-27), Blank-SAP (Cat. #IT-21)
PARVing the way to cap translation for seizure control
Gross C (2021) PARVing the way to cap translation for seizure control. Epilepsy Curr 21(5):360-362. doi: 10.1177/15357597211027010
Summary: Loss of GABAergic interneurons leads to spontaneous recurrent seizures that persist over months if the amount and spatial spread of initial inhibitory neuron loss is sufficient.
Usage: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.
Related Products: SSP-SAP (Cat. #IT-11)