control-conjugates

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.

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

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 69(1):121-129. doi: 10.2478/jvetres-2025-0003 PMID: 40144066

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.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

See Also:

• Aerts EG et al. The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287, 2024.

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.

Related Products: Neurotensin-SAP (Cat. #IT-56), Blank-SAP (Cat. #IT-21)

Turner KL, Brockway DF, Hossain MdS, Griffith KR, Greenwalt DI, Zhang Q, gheres KW, Crowley NA, Drew PJ (2025) type-I nNOS neurons orchestrate cortical neural activity and vasomotion. bioRxiv 2025.01.21.634042. doi: 10.1101/2025.01.21.634042 PMID: 39896560

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).

Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)

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 (2025) 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 30(6):2381-2394. 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.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

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).

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #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).

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

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).

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)

Jiang H, Cui H, Chen M, Li F, Shen X, Guo CJ, Hoekel GE, Zhu Y, Han L, Wu K, Holtzman MJ, Liu Q (2024) Divergent sensory pathways of sneezing and coughing. Cell 187(21):5981-5997. doi: 10.1016/j.cell.2024.08.009 PMID: 39243765

Objective: To study the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing.

Summary: Sneezing and coughing are frequently associated with allergies and respiratory viral infections and it’s assumed both involve common sensory receptors and neurotransmission mechanisms. The author’s work show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3−) mediates sneezing. Although this same population innervates the trachea, it does not mediate coughing, and instead, a distinct sensory population (somatostatin SST) mediates coughing but not sneezing. NMB-SAP was used to ablate neruomedin B (NMB) receptor expressing and nucleus tractus solitarius (NTS) neurons. Deletion of these neurons did not affect the coughing responses to Ly344864 and IL-31 (agonists to SST neurons) suggesting that NMB-sensitive NTS neurons do not mediate coughing.

Usage: Neuronal ablation by SST-saporin and NMB-saporin. SST-saporin was made by mixing biotin-labeled somatostatin and Streptavidin-ZAP (IT-27) at a 1:1 molar ratio at room temperature for 20 minutes. SST-Saporin (10 μM, 50 nL), NMB-saporin (#IT-70; 50 ng in 50 nL) or Blank-SAP (#IT-21; 10 μM in 50 nL or 50 ng in 50 nL) was injected into the NTS region.

Related Products: Streptavidin-ZAP (Cat. #IT-27), NMB-SAP (Cat. #IT-70), Blank-SAP (Cat. #IT-21)

Guo SS, Gong Y, Zhang TT, Su XY, Wu YJ, Yan YX, Cao Y, Song XL, Xie JC, Wu D, Jiang Q, Li Y, Zhao X, Zhu MX, Xu TL, Liu MG (2024) A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch. Sci Adv 10(33):eadn6272. doi: 10.1126/sciadv.adn6272 PMID: 39150998

Objective: To investigate anxiety-like behaviors in mouse models of chronic itch and identify lateral septum (LS) GABAergic neurons as key mediators through thalamic and hypothalamic circuit interactions.

Summary: Chronic itch amplifies excitatory inputs from the thalamic nucleus reuniens to LS GABAergic neurons, promoting anxiety-like behaviors. Inhibiting the Re → LS circuit reduces anxiety related to chronic itch but not restraint stress, highlighting its specificity. LS GABAergic neurons suppress lateral hypothalamus activity to mediate chronic itch-induced anxiety, with Bombesin-SAP targeting spinal itch neurons to confirm this pathway’s role.

Usage: Mice were intrathecally injected with Bombesin-SAP (IT-40) (400 ng/5 μl). Blank-SAP (IT-21) (400 ng/5 μl) was administered similarly to a control.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)