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
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).
Lee H, Hor CC, Horwitz LR, Xiong A, Su XY, Soden DR, Yang S, Cai W, Zhang W, Li C, Radcliff C, Dinh A, Fung TLR, Rovcanin I, Pipe KP, Xu XZS, Duan B (2025) A dedicated skin-to-brain circuit for cool sensation in mice. Nat Commun 16(1):6731. doi: 10.1038/s41467-025-61562-y PMID: 40721582
Objective: To investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
Summary: The study identifies Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation reveal distinct sensory processing roles for various neuronal subtypes.
Usage: Bombesin-SAP (IT-40), or control conjugate Blank-SAP (IT-21), was administered intrathecally at a dose of 400 ng in 10 μL sterile saline to ablate GRPR+ spinal neurons and assess their role in sensory behavior.
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.
Morishata Y, Fuentes I, Gonzalez-Salinas S, Favate J, Mejaes J, Zushida K, Nishi A, Hevi C, Goldsmith N, Buyske S, Sillivan SE, Miller CA, Kandel ER, Uchida S, Shah P, Alarcon JM, Barker DJ, Shumyatsky GP (2024) Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction. Molexular Psychiatry doi: 10.1038/s41380-024-02843-8 PMID: 39580604
Objective: To investigate neural circuits serving the dopamine function for fear extinction and PTSD.
Summary: Results demonstrate that gastrin-releasing peptide regulates dopamine function in stress-enhanced fear processing and identifies Grp as the first gene known to regulate dopaminergic control of fear extinction.
Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) (80 ng/µl) dissolved in saline were injected bilaterally into the basolateral amygdala (AP: -2.0 mm, ML: ±3.25 mm, DV: -4.3 mm) in 0.3 µl volume.
Rehal SK (2024) Investigating the role of the ventral anterior cingulate cortex (vacc) in placebo analgesia. Univ Toronto Thesis.
Objective: To examine whether opioid receptors in the ventral anterior cingulate cortex (vACC) were critical for the placebo response evoked by conditioning with 10 mg/kg morphine.
Summary: Significant differences were observed before and after injection of morphine for Dermorphin-SAP-treated mice throughout the conditioning days. At the same time, a percentage of anti-allodynia remained constant over the conditioning phase. Thus, mice displayed the analgesic effects of morphine during the conditioning phase. Additionally, microinjection of Dermorphin-SAP into the vACC did not influence pharmacological conditioning with morphine as there was no difference between either group during the conditioning phase. Selective ablation of mu opioid-expressing neurons in the vACC via Dermorphin-SAP led to a lack of placebo analgesia.
Usage: Bilateral injections were carried out at a rate of 50 nl/min of Dermorphin-SAP (IT-12) or 200 nl total injection volume of Blank-SAP control (IT-21).
Chuang KH, Zhou XA, Xia Y, Li z, Qian L, Eeles E, Ngiam G, Fripp J, Coulson EJ (2024) Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux. bioRxiv 2024.08.25.609536. doi: 10.1101/2024.08.25.609536
Objective: To show that vascular-CSF coupling correlates with cortical cholinergic activity in non-demented aged humans.
Summary: Waste from the brain is cleared via a cerebrospinal fluid (CSF) exchange pathway. Problems in this pathway is suggested to underlie the pathogenesis of many brain conditions. Cerebrovascula oscillation that couples with pulsatile CSF inflow is suggested to drive the flow of fluid, however how this coupling is regulated in unlcear. The resultsfor the study suggest a neurovascular mechanism by which CSF/glymphatic flux is modulated by cholinergic neuronal activity, thereby providing a conceptual basis for the development of diagnostics and treatments for glymphatic dysfunction.
Usage: Injections of mu-p75-SAP (0.5 mg/ml, IT-16) or control Rabbit-IgG-SAP (0.5 mg/ml, IT-35) were performed into the border between the medial septum and ventral diagonal band. In the first study, the toxin was infused at a rate of 0.4 μl/min (1.5μl total volume), which resulted in a large amount of ablation. In the second study, the toxin concentration was reduced to 0.3 mg/ml to preserve more cholinergic neurons and was infused at a rate of 0.18μl/min (1.0μl total volume).
Blanco T, Nakagawa H, Musayeva A, Krauthammer M, Singh RB, Narimatsu A, Ge H, Shoushtari SI, Dana R (2024) Acquired immunostimulatory phenotype of migratory CD103+ DCs promotes alloimmunity following corneal transplantation. JCI Insight 9(20):e182469. doi: 10.1172/jci.insight.182469 PMID: 39235864
Objective: To investigate the interaction between antigen-presenting cell subsets, specifically CD11b+ dendritic cells (DC2) and CD103+ dendritic cells (DC1),in the context of transplant immunity.
Summary: The findings highlight the critical role of CD103+ DC1 in modulating host alloimmune responses. In recipients with uninflamed corneal beds, migratory CD103+ DC1 exhibit a tolerogenic phenotype. These cells influence the immunogenic behavior of CD11b+ DC2 primarily through IL-10 production, suppressing alloreactive CD4+ Th1 cells via the PD-L1/PD-1 pathway and promoting Treg-mediated tolerance through αvβ8 integrin–activated TGF-β1. Together, these mechanisms contribute to improved graft survival.
Usage: In vivo depletion of CD103+ DC1: Recipient BALB/c or RAG-/- mice were administered 2.0 mg/kg of Anti-CD103-SAP (IT-50) intraperitoneally, or an equivalent dose of control conjugate (IgG-SAP).
