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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
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)
Investigating the role of the ventral anterior cingulate cortex (vacc) in placebo analgesia
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)
Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux
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)
Acquired immunostimulatory phenotype of migratory CD103+ DCs promotes alloimmunity following corneal transplantation
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)
Divergent sensory pathways of sneezing and coughing
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)
A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch
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)
Striatal parvalbumin interneurons are activated in a mouse model of cerebellar dystonia
Matsuda T, Morigaki R, Hayasawa H, Koyama H, Oda T, Miyake K, Takagi Y (2024) Striatal parvalbumin interneurons are activated in a mouse model of cerebellar dystonia. Dis Model Mech 17(5):dmm050338. doi: 10.1242/dmm.050338 PMID: 38616770
Objective: To examine the influence of cerebellar abnormalities on the basal ganglia circuitry to investigate dystonia pathophysiology.
Summary: Dystonia is a disorder characterized by twisting, repetitive movements, and abnormal postures induced by sustained muscle contractions. This study utilized a cerebellar dystonia mouse model to examine the cerebellum’s contribution. The authors found that modulating parvalbumin (PV) interneurons might provide a novel treatment strategy.
Usage: In order to selectively ablate dorsolateral striatal PV interneurons, Streptavidin-ZAP (Cat. #IT-27) was mixed equimolar with biotinylated anti-PV and diluted with PBS by 1:100 and 3 ul injected into the striatum of mice. BIgG-SAP Rabbit (Cat. #IT-75) was used as the control.
Related Products: Streptavidin-ZAP (Cat. #IT-27), BIgG-SAP Rabbit (Cat. #IT-75)
Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding
Choi PP, Wang Q, Brenner LA, Li AJ, Ritter RC, Appleyard SM (2024) Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding. Endocrinology 165(5):bqae021. doi: 10.1210/endocr/bqae021 PMID: 38368624
Objective: To explore the role of NPY receptor-expressing neurons in regulating feeding behavior in rats.
Summary: In response to glucose deficits, rats exhibit counter-regulatory mechanisms to stimulate feeding. To clarify the role of NPY-sensitive neurons, these neurons were selectively ablated using NPY-SAP. The results showed that while Saporin-lesioned rats exhibited reduced 2DG-induced feeding, there was no impact on 2DG-induced locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release.
Usage: NPY-SAP [IT-28] or Blank-SAP [IT-21] (50 ng per 100nL/site) was used to specifically lesion NPY receptor-expressing neurons in the perifornical lateral hypothalamus of male rats.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Brainstem DBH+ neurons control chronic allergen-induced airway hyperreactivity
Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nammerjahn A, Sun X (2024) Brainstem DBH+ neurons control chronic allergen-induced airway hyperreactivity. bioRxiv 2023.02.04.527145. doi: 10.1101/2023.02.04.527145 PMID: 36778350
Summary: The authors show that a single population of Dbh+ neurons in the nucleus of the solitary tract (nTS) of the brainstem, and downstream neurons in the nucleus ambiguous (NA), are both necessary and sufficient for chronic allergen-induced airway hyperreactivity. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity. This opens the possibility of targeted neural modulation as an approach to control refractory allergen- induced airway constriction.
Usage: Anti-DBH-SAP (IT-03) was injected stereotactically into both sides of the nTS of wild-type mice (42 ng/200 nL). Blank-SAP (IT-21) was used as control.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Blank-SAP (Cat. #IT-21)
The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep
Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) 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. doi: 10.1093/biolre/ioad147 PMID: 37930247
Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.
Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.
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)
