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196 entries

Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice

Chen CH, Tsai TC, Wu YJ, Hsu KS (2023) Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice. JCI Insight e161874. doi: 10.1172/jci.insight.161874 PMID: 37200091

Objective: This study aimed to characterize gut-to-brain signaling and brain circuitry responsible for anxiety-like behaviors in a mouse model of inflammatory bowel disease.

Summary: The researchers found that mice with experimental colitis induced by dextran sulfate sodium administration displayed increased anxiety-like behaviors, which were prevented by cutting the vagus nerve connecting the gut to the brain. Further experiments showed that silencing brain cells in the locus coeruleus that project to the basolateral amygdala reduced anxiety behaviors in the colitis mice.

Usage: CCK-SAP (250 ng/µl) or Blank-SAP (250 ng/µl) were unilaterally or bilaterally injected to rostral (0.5 µl) and caudal (0.5 µl) parts of the nodose ganglia using a beveled injection pipette controlled by a microprocessor-controlled injector at the speed of 50 nl/sec.

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis

Madrid LI, Bandhavkar S, Hafey K, Jimenez-Martin J, Milne M, Coulson EJ, Jhaveri DJ (2022) Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis. bioRxiv 2022.08.25.505357. doi: 10.1101/2022.08.25.505357

Objective: To investigate the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippocampus and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons.

Summary: This work reveals stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippocampal neurogenesis.

Usage: Medial septum cholinergic lesion was achieved by infusion of mu p75-SAP (0.4 µg/µl). Rabbit IgG-SAP (0.4 µg/µl) was used as control.

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

Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior

Krieger JP, Asker M, Van der Velden P, Börchers S, Richard JE, Maric I, Longo F, Singh A, De Larigue G, Skibicka KP (2022) Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biological Psychiatry in press. doi: 10.1016/j.biopsych.2022.04.020

Objective: To determine how the sensing of gastrointestinal state affects anxiety.

Summary: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. The article results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety.

Usage: 1.5 ul of CCK-SAP or Blank-SAP were delivered into each nodose ganglion at 250 ng/ul.

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Featured Article: Selective ablation of IB4+ primary afferent neurons reduces mechanical and cold hyperalgesia in an EAE mouse model of multiple sclerosis

Nguyen KL, Lamerand SR, Deshpande RP, Taylor BK (2021) Featured Article: Selective ablation of IB4+ primary afferent neurons reduces mechanical and cold hyperalgesia in an EAE mouse model of multiple sclerosis. Targeting Trends 22

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

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Oxytocin-conjugated saporin injected into the substantia nigra of male rats alters the activity of the nigrostriatal dopaminergic system: A behavioral and neurochemical study

Sanna F, Bratzu J, Angioni L, Pina Sorighe M, Cocco C, Argiolas A, Melis MR (2021) Oxytocin-conjugated saporin injected into the substantia nigra of male rats alters the activity of the nigrostriatal dopaminergic system: A behavioral and neurochemical study. Brain Res 1773:147705. doi: 10.1016/j.brainres.2021.147705 PMID: 34744015

Objective: To investigate the effects of Oxytocin-SAP in the substantia nigra of male rats, and assess its impact on nigral Tyrosine Hydroxylase-immunoreactivity, dopamine content, locomotor activity, rotational turning, and striatal dopamine function.

Summary: Researchers investigated the effects of injecting oxytocin-conjugated Saporin into the substantia nigra of male rats. They found that this treatment led to changes in the activity of the nigrostriatal dopaminergic system, as evidenced by alterations in behavior and neurochemical markers associated with dopamine function.

Usage: Oxytocin-SAP (60 ng/μl and 120 ng/μl) was injected unilaterally into the substantia nigra of male rats, respectively, compared to Blank-SAP.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Cholinergic modulation of sensory processing in awake mouse cortex

Jimenez-Martin J, Potapov D, Potapov K, Knöpfel T, Empson RM (2021) Cholinergic modulation of sensory processing in awake mouse cortex. Sci Rep 11(1):17525. doi: 10.1038/s41598-021-96696-8

Objective: To decipher the timing and significance of acetylcholine actions.

Summary: Study provides new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

Usage: Focal cortical injection of mu p75-SAP or Rabbit IgG-SAP (1.7 mg/ml, 0.3 µl total volume, rate 0.075 µl/minute).

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

The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

Maejima Y, Yokota S, Shimizu M, Horita S, Kobayashi D, Hazama A, Shimomura K (2021) The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity. Nutr Metab (Lond) 18(1):58. doi: 10.1186/s12986-021-00582-z

Summary: Feeding rhythm disruption contributes to the development of obesity. GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination.

Usage: Exenatide-SAP targets GLP-1R expressing cells. Injections of 0.1 μg/0.5 μl Ex4-SAP or 0.1 μg/0.5 μl Blank-SAP (control) were administered into the DMH.

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-SAP (Cat. #IT-21)

An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol’s dopamine-releasing effect.

Loftén A, Adermark L, Ericson M, Söderpalm B (2021) An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol’s dopamine-releasing effect. Addict Biol 26(3):e12959. doi: 10.1111/adb.12959

Summary: Basal extracellular levels of dopamine within the nucleus accumbens are not sustained by muscarinic acetylcholine, whereas accumbal Cholinergic interneurons-ACh are involved in mediating ethanol-induced dopamine release.

Usage: Anti-ChAT-SAP or Rabbit IgG-SAP were infused at a flow rate of 0.05 μl/min for 10 min giving a total volume of 0.5 μl.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition

Wang Z, Jiang C, Yao H, Chen O, Rahman S, Gu Y, Zhao J, Huh Y, Ji RR (2021) Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition. Brain 144(2):665-681. doi: 10.1093/brain/awaa430

Summary: Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of Bombesin-SAP.

Usage: For ablation of GRPR+ neurons, mice were given an intrathecal injection of 400 ng Bombesin-SAP or Blank-SAP (control) 10 days before behavioral testing.

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

Identification of prostaglandin F2 receptor negative regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development

Marquez J, Dong J, Dong C, Tian C, Serrero G (2021) Identification of prostaglandin F2 receptor negative regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development. PLoS One 16(1):e0246197. doi: 10.1371/journal.pone.0246197

Summary: PTGFRN is a cell-surface protein that is upregulated in certain cancer types, including head and neck and, notably, pediatric medulloblastoma, an aggressive cancer with limited therapeutic options. With the selection of the mouse monoclonal antibody 33B7, the authors identified PTGFRN as a potential therapy target, and show that it is internalized by incubation with 33B7. Purified 33B7 antibody was sent to Advanced Targeting Systems where saporin was directly conjugated to the Fc region of 33B7 using their proprietary cleavable linker.

Usage: In a 96-well plate, 2000 cells/well were plated in triplicate in 100 μL of DMEM/F12 medium supplemented with 2.5% FBS, 0.4 ug/ml 33B7 antibody, and 0.9ug/ml of Fab-ZAP mouse. As an isotype control, cells were incubated with mouse Fab IgG-SAP as control (instead of 33B7) and Fab-ZAP.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Fab IgG-SAP (Cat. #IT-67), Custom Conjugates

BNP facilitates NMB-mediated histaminergic itch via NPRC-NMBR crosstalk

Meng QT, Liu XY, Liu XT, Barry DM, Jin H, Sun Y, Yang Q, Wan L, Jin JH, Shen kF, Munanairi A, Kim R, Yin J, Tao A, Chen ZF (2021) BNP facilitates NMB-mediated histaminergic itch via NPRC-NMBR crosstalk. bioRxiv 2021.01.26.428310. doi: 10.1101/2021.01.26.428310

Related Products: Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)

Oxytocin influences male sexual activity via non-synaptic axonal release in the spinal cord.

Oti T, Satoh K, Uta D, Nagafuchi J, Tateishi S, Ueda R, Takanami K, Young LJ, Galione A, Morris JF, Sakamoto T, Sakamoto H (2021) Oxytocin influences male sexual activity via non-synaptic axonal release in the spinal cord. Curr Biol 31(1):103-114.e5. doi: 10.1016/j.cub.2020.09.089

Summary: Oxytocin directly activates SEG (Spinal Ejaculation Generator)/GRP (Gastrin-Releasing Peptide) neurons via OXTRs (Oxytocin Receptors) and influences male sexual function in the rat lumbar spinal cord.

Usage: Oxytocin-SAP (4 or 40 ng) was infused slowly into the L3 and L4 spinal cord. Blank-SAP was used as control.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss

Tapa S, Wang L, Francis Stuart SD, Wang Z, Jiang Y, Habecker BA, Ripplinger CM (2020) Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss. Sci Rep 10:18801. doi: 10.1038/s41598-020-75903-y

Summary: The authors present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing Anti-DBH-SAP.

Usage: Either 5μL of 40 ng/μL Anti-DBH-SAP or Mouse IgG-SAP (control) was applied three times directly to the exposed apical/anterior surface of the heart.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Antibody-drug conjugates targeting CD45 plus Janus kinase inhibitors effectively condition for allogeneic hematopoietic stem cell transplantation

Persaud SP, Ritchey JK, Choi J, Ruminski PG, Cooper ML, Rettig MP, DiPersio JF (2020) Antibody-drug conjugates targeting CD45 plus Janus kinase inhibitors effectively condition for allogeneic hematopoietic stem cell transplantation. bioRxiv 2020.10.02.324475. doi: 10.1101/2020.10.02.324475

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

Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis.

Liu X, Wang D, Wen Y, Zeng L, Li Y, Tao T, Zhao Z, Tao A (2020) Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis. J Invest Dermatol 140(9):1856-1866.e7. doi: 10.1016/j.jid.2020.01.016

Objective: The authors investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE).

Summary: Targeting gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) may provide effective treatments for ACD associated chronic pruritus.

Usage: A single dose of Bombesin-SAP (400 ng) and Blank-SAP (400 ng) or two doses of Nppb-SAP (BNP-SAP; 650 ng) and Blank-SAP (650 ng) were administered via intrathecal injection.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)

GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn.

Kiguchi N, Uta D, Ding H, Uchida H, Saika F, Matsuzaki S, Fukazawa Y, Abe M, Sakimura K, Ko MC, Kishioka S (2020) GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn. Neuropharmacology 170:108025. doi: 10.1016/j.neuropharm.2020.108025

Objective: To investigate the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH).

Summary: These findings demonstrate that GRP and glutamate cooperatively regulate GRPR+ AMPAR+ neurons in SDH, mediating itch sensation. GRP–GRPR and the glutamate–AMPAR system may play pivotal roles in the spinal transmission of itch in rodents and nonhuman primates.

Usage: Bombesin-SAP and Blank-SAP were administered i.t. (5 μg/5 μl).

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

Loss of leptin receptor-expressing cells in the hindbrain decreases forebrain leptin sensitivity.

Harris RBS (2020) Loss of leptin receptor-expressing cells in the hindbrain decreases forebrain leptin sensitivity. Am J Physiol Endocrinol Metab 318(5):E806-E816. doi: 10.1152/ajpendo.00020.2020

Objective: This study tested whether loss of hindbrain leptin receptor signaling changed sensitivity to forebrain leptin.

Summary: Loss of VMH (ventromedial nucleus of hippocampus) leptin receptor-expressing cells prevents weight loss. The integrated response between the hindbrain and forebrain is heavily dependent upon leptin activity in the VMH.

Usage: To test forebrain leptin sensitivity Leptin-SAP and Blank-SAP rats received third ventricle injections of 0, 0.05, 0.1, 0.25 or 0.5 μg leptin.

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

Cholinergic basal forebrain degeneration due to obstructive sleep apnoea increases Alzheimer’s pathology in mice.

Qian L, Kasas L, Milne MR, Rawashdeh O, Marks N, Sharma A, Bellingham MC, Coulson EJ (2020) Cholinergic basal forebrain degeneration due to obstructive sleep apnoea increases Alzheimer’s pathology in mice. bioRxiv 2020.03.12.989848. doi: 10.1101/2020.03.12.989848

Usage: bilateral injections of urotensin II-saporin (UII-SAP; 0.07 μg/μL per site – unless stated otherwise; generous gift from Advanced Targeting Systems)

Related Products: Custom Conjugates, Blank-SAP (Cat. #IT-21)

Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors.

Bernabe CS, Caliman IF, Truitt WA, Molosh AI, Lowry CA, Hay-Schmidt A, Shekhar A, Johnson PL (2020) Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors. J Psychopharmacol 34(4):400-411. doi: 10.1177/0269881119900981

Objective: To investigate the role of amygdala-projecting 5-HT neurons in the DR in innate anxiety and conditioned fear behaviors.

Summary: The studies support the hypothesis that amygdala-projecting 5-HT neurons in the DR represent an anxiety and fear-on network.

Usage: Each rat received two bilateral microinjections per site (100 nL each, 1 μM in artificial cerebrospinal fluid) of either Anti-SERT-SAP or the control Mouse IgG-SAP.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Inflammatory macrophages facilitate mechanical stress-induced osteogenesis.

Zhang F, Huan L, Xu T, Li G, Zheng B, Zhao H, Guo Y, Shi J, Sun J, Chen A (2020) Inflammatory macrophages facilitate mechanical stress-induced osteogenesis. Aging (Albany NY) 12(4):3617-3625. doi: 10.18632/aging.102833

Summary: In a mouse model of distraction osteogenesis (DO), there was significant increase in macrophages in the regeneration area. This suggests that targeting inflammatory macrophages may help to improve clinical bone repair.

Usage: For saporin-mediated depletion of macrophages, DO-surgery-treated mice received an intraventricular (iv) injection of either Mac-1-SAP or Rat IgG-SAP (20µg) once every 3 days.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Rat IgG-SAP (Cat. #IT-17)

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