Herrerias A, Oliverio A, Dvorácskó S, Thyagarajan A, Chedester L, Liu J, Cinar R, Iyer MR, Kunos G, Godlewski G (2025) CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice. Mol Psychiatry doi: 10.1038/s41380-025-03266-9 PMID: 40975751
Objective: To investigate how peripheral CB1 receptors on vagal afferent neurons regulate voluntary ethanol intake and their role in gut-brain signaling underlying alcohol consumption.
Summary: Selective deletion or ablation of CB1R in nodose ganglion neurons abolished the inhibitory effects of peripheral CB1R antagonists on voluntary ethanol intake. The study identifies CB1R on Gpr65⁺ vagal sensory neurons as critical mediators of gut-brain communication regulating alcohol preference and intake.
Usage: Anti-CB1-SAP (IT-104) or Blank-SAP (IT-21) was injected into the proximity of the nodose ganglion at 250 ng/mL to selectively ablate CB1R-expressing vagal afferent neurons
Kobayashi K, Miyazaki Y, Sakamoto N, Yamamoto M, Nagat N, Murata T (2025) Long-term scratching analysis of mice using machine learning. PNAS Nexus pgaf292. doi: 10.1093/pnasnexus/pgaf292
Objective: To objectively quantify mouse scratching behavior across light and dark cycles using automated, long-term machine learning analysis.
Summary: Naïve BALB/c mice exhibited more frequent and persistent scratching during the light period, and DNFB-induced dermatitis caused biphasic, long-lasting scratching even during rest. The study establishes a continuous behavior analysis method that reveals circadian and pathological pruritus features.
Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at 400 ng in 5 μL PBS.
Hor CC (2025) The dual nature of cold: Unraveling the neural circuits for cool sensing and cold allodynia. Univ Michigan
Objective: To elucidate the neural mechanisms underlying innocuous cool sensation from the skin to the brain and the spinal circuitry changes that drive cold allodynia under pathological conditions.
Summary: The study identified distinct spinal interneuron populations mediating innocuous cool sensation (Trhr⁺ neurons) and cold allodynia (Tac1⁺/Calb1⁺ neurons). Ablation of these neurons demonstrated their modality-specific contributions, with Trhr⁺ interneurons responsible for cool detection and Tac1⁺/Calb1⁺ neurons for pathological cold hypersensitivity, revealing a spinal circuit basis for temperature discrimination and pain plasticity.
Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at a single dose of 400 ng in 10 µL sterile saline to ablate spinal GRPR⁺ neurons involved in thermal and itch processing.
Kolahdouzan M, Ghazisaeidi S, Tu Y, Muley M, Gambeta E, Salter M (2025) Meningeal macrophages mask incision pain sensitization in male rats. Mol Pain doi: 10.1177/17448069251383593
Objective: To investigate whether CD206+macrophages in the meninges play a role in regulating nociception and pain hypersensitivity.
Summary: The results indicate that while CD206+ meningeal macrophages do not regulate basal nociception in naïve rats, they mask mechanical hypersensitivity in male rats after skin incision injury. Thus, we conclude that in a sex-dependent manner, CD206+ meningeal macrophages prevent the spread of pain hypersensitivity after a minor injury.
Usage: Rats were injected intrathecally (30 μl) with saline, CD206-Saporin (20 μg mannose-receptor antibody and 7 μg of Streptavidin-ZAP in 30 μl), or Rabbit-IgG-Saporin (control).
Noh M, Corrigan KA, Williams SG, Peirs C, Leone MJ, Headrick DJ, Guvercin M, Lee S, Phan BN, Yeramosu D, Babu S, Brown AR, Van De Weerd R, Zhao X, Dunn RP, Mathys H, Pfenning AR, Seal RP (2025) A molecular and spinal circuit basis for the functional segregation of itch and pain. bioRxiv 2025.07.31.667966. doi: 10.1101/2025.07.31.667966
Objective: To define how distinct subtypes of Grpr⁺ dorsal horn neurons contribute to itch and pain processing and to demonstrate the utility of genomic enhancer-based strategies for modality-specific targeting.
Summary: The study revealed two functionally distinct Grpr⁺ neuron subtypes: Tac1⁻ neurons mediate itch, while Tac1⁺ neurons mediate mechanical allodynia. Selective silencing or ablation of each subtype modulated only its respective sensory behavior, illustrating clear modality segregation within the dorsal horn circuitry.
Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally (300 ng) to selectively ablate Grpr⁺ neurons
We are highlighting one of our saporin conjugates, Bombesin-SAP. A tool for depleting cells that express gastrin releasing peptide receptor (GRPR). Bombesin is a 14-amino acid peptide actually found in frog skin. The human equivalent GRP has been detected in itch pathways and plays a role in eating behaviors.
Their objective was to investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
The authors were able to administer Bombesin-SAP (IT-40) or a control conjugate (Blank-SAP, IT-21) intrathecally to ablate GRPR-positive spinal neurons to assess their role in sensory behavior.
In their study, they identified Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation revealed distinct sensory processing roles for various neuronal subtypes.
Noble EE, Harris RBS (2025) Leptin in the VMH contributes to the initial overconsumption of palatable diets by rats. Am J Physiol Endocrinol Metab 329(1):E1-E17. doi: 10.1152/ajpendo.00090.2025 PMID: 40418155
Objective: To determine whether leptin receptor–expressing neurons in the ventromedial hypothalamus (VMH) contribute to the initial overconsumption of a high-fat diet in rats.
Summary: Ablation of VMH leptin receptor–expressing neurons using Leptin-SAP prevented the early hyperphagic response to a high-fat diet in male rats but had no long-term impact on energy intake, body weight, or glucose clearance. These findings suggest VMH leptin signaling plays a key role in initiating, but not maintaining, diet-induced hyperphagia.
Usage: Leptin-SAP (IT-47) or Blank-SAP (IT-21) was stereotaxically injected into the VMH of male and female rats (20 ng in 80 nL) to ablate leptin receptor–expressing neurons. This targeted lesion confirmed the role of VMH leptin signaling in mediating early-phase overeating in response to a high-fat diet.
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 doi: 10.2478/jvetres-2025-0003
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.
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.
Objective: To uncover the role of a sparse but unusual population of genetically-distinct interneurons known as type-I nNOS neurons, using a novel pharmacological strategic to unilaterally ablate these neurons from the somatosensory cortex of mice.
Summary: Region-specific ablation produced changes in both neural activity and vascular dynamics, decreased power in the delta-band of the local field potential, reduced sustained vascular responses to prolonged sensory stimulation, and abolished the post-stimulus undershoot in cerebral blood volume. Coherence between the left and right somatosensory cortex gamma-band power envelope and blood volume at ultra-low frequencies was decreased, suggesting type-1 nNOS neurons integrate long-range coordination of brain signals. Authors also observed decreases in the amplitude of resting-state blood volume oscillations and decreased vasomotion following the ablation of type-I nNOS neurons.
Usage: Type-I nNOS neurons were selectively ablated with saporin conjugated to a substance P analog (SP-SAP, IT-07). Intracortical injection with 4 ng of either SAP conjugate or Blank-SAP (IT-21).
