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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)
Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin.
Goodman RL, He W, Lopez JA, Bedenbaugh MN, McCosh RB, Bowdridge EC, Coolen LM, Lehman MN, Hileman SM (2019) Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin. Endocrinology 160(12):2990-3000. doi: 10.1210/en.2019-00597
Objective: To determine if NKB is involved in the RCh of the ewe in the LH surge.
Summary: NKB signaling in the RCh increases kisspeptin levels critical for the full amplitude of the LH surge in the ewe, but kisspeptin release occurs independently of retrochiamatic area (RCh) input at the onset of the surge to initiate GnRH secretion.
Usage: Bilaterial injections in the RCh of either NK3-SAP or Blank-SAP.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
OP11: Role of spinal cholecystokinin receptor 2 in alloknesis models.
Tominaga M, Kusube F, Honda K, Komiya E, Takahashi N, Naito H, Suga Y, Takamori K (2019) OP11: Role of spinal cholecystokinin receptor 2 in alloknesis models. Itch 4:1-62. doi: 10.1097/itx.0000000000000030
Objective: To determine the detailed molecular and cellular mechanisms that induce alloknesis via the spinal CCK2 receptor.
Summary: Ablation of spinal CCK receptor-expressing cells by i.t. injection of CCK-SAP attenuated CCK8S-induced alloknesis in comparison with Blank-SAP control mice.
Usage: Intrathecal injection
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions.
Seamon M, Ahn W, Li AJ, Ritter S, Harris RBS (2019) Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. Am J Physiol Endocrinol Metab 317(4):E586-E596. doi: 10.1152/ajpendo.00205.2019
Objective: To test the importance of VMH leptin responsiveness in mediating weight loss caused by fourth ventricle leptin infusion.
Summary: Leptin did not inhibit food intake and respiratory exchange ratio in rats treated with Leptin-SAP. VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions, but limit weight gain during positive energy balance.
Usage: Bilateral VMH 75-nl injections of 260 ng/ml of Leptin-SAP or Blank-SAP.
Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)
Identification of a spinal circuit for mechanical and persistent spontaneous itch.
Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, Hor CC, Zaher N, Cin M, Slade H, Huang T, Xu XZS, Duan B (2019) Identification of a spinal circuit for mechanical and persistent spontaneous itch. Neuron 103(6):1135-1149.e6. doi: 10.1016/j.neuron.2019.06.016
Objective: To identify a spinal circuit for mechanical and persistent spontaneous itch.
Summary: Findings indicate excitatory interneurons expressing Urocortin 3::Cre (Ucn3+) in the dorsal spinal cord as a valid cellular target for future therapeutic interventions against chronic itch, without affecting normal touch.
Usage: To ablate spinal GRPR+ neurons, mice were given a single intrathecal injection of either Bombesin-SAP or Blank-SAP (400 ng in 10 mL sterile saline). To ablate spinal Npra+ neurons, mice were given a single intrathecal injection of either Nppb-SAP or Blank-SAP (5 mg in 10 mL sterile saline).
Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)
Central glucagon-like peptide-1 receptor signaling via brainstem catecholamine neurons counteracts hypertension in spontaneously hypertensive rats.
Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS, Sharma NM, Patel KP, Kario K, Yada T (2019) Central glucagon-like peptide-1 receptor signaling via brainstem catecholamine neurons counteracts hypertension in spontaneously hypertensive rats. Sci Rep 9(1):12986. doi: 10.1038/s41598-019-49364-x
Objective: To determine mechanisms for antihypertensive effect of GLP-1R agonists.
Summary: The central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.
Usage: Anti-DBH-SAP or Blank-SAP was injected into NTS bilaterally (6 ng/200 nl).
Related Products: Anti-DBH-SAP (Cat. #IT-03), Blank-SAP (Cat. #IT-21)
The undeveloped properties of GABA neurons in the ventral tegmental area promote energy intake for growth in juvenile rats.
Maejima Y, Yokota S, Horita S, Shimomura K (2019) The undeveloped properties of GABA neurons in the ventral tegmental area promote energy intake for growth in juvenile rats. Sci Rep 9(1):11848. doi: 10.1038/s41598-019-48336-5
Objective: To determine the underlying mechanisms that induce high energy intake (EI) per body weight (BW).
Summary: Undeveloped properties of VTA GABA neurons in juvenile rats can promote higher EI regardless of high or less palatable feeding, and contribute to growth promotion.
Usage: GAT1-SAP or control, Rabbit IgG-SAP, was bilaterally injected (0.025 μg/0.5 μl) into the VTA in eight-week-old adult rats.
Related Products: GAT1-SAP (Cat. #IT-32), Rabbit IgG-SAP (Cat. #IT-35)
Selective role of neurokinin B in IL-31–induced itch response in mice.
Sakata D, Uruno T, Matsubara K, Andoh T, Yamamura K, Magoshi Y, Kunimura K, Kamikaseda Y, Furue M, Fukui Y (2019) Selective role of neurokinin B in IL-31–induced itch response in mice. J Allergy Clin Immunol 144(4):1130-1133. doi: 10.1016/j.jaci.2019.06.031
Objective: To examine the physiological significance of neurokinin B in IL-31–induced itch sensation.
Summary: IL-31–induced scratching was unaffected by intrathecal injection of Nppb-SAP. In contrast,treatment with Bombesin-SAP reduced IL-31–induced scratching. Neurokinin B acts upstream of GRP to transmit IL-31–induced itch sensation.
Usage: Intrathecal injection
Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21), NKB-SAP (Cat. #IT-63)
Spinal neuropeptide Y1 receptor-expressing neurons form an essential excitatory pathway for mechanical itch.
Acton D, Ren X, DiCostanzo S, Dalet A, Bourane S, Bertocchi I, Eva C, Goulding M (2019) Spinal neuropeptide Y1 receptor-expressing neurons form an essential excitatory pathway for mechanical itch. Cell Reports 28(3):625-639.e6 . doi: 10.1016/j.celrep.2019.06.033
Objective: To determine the central pathway for mechanical itch.
Summary: NPY-Y1 signaling regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes. Neither the evoked nor spontaneous scratching seen following activation of Y1Cre neurons was affected by ablation of the GRPR+ neurons. NK1R+ neuron ablation failed to modulate mechanically evoked itch.
Usage: P28 mice were given a single intrathecal (i.t.) injection of either Bombesin-SAP (400 ng in 5 mL 0.9% sterile saline) to ablate GRPR+ cells or SSP-SAP to ablate NK1r+ neurons (100 ng in 5 mL 0.9% sterile saline). Littermate controls received Blank-SAP (equal mass in 5 mL 0.9% sterile saline).
Related Products: Bombesin-SAP (Cat. #IT-40), SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)
Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
Weiner GA, Shah SH, Angelopoulos CM, Bartakova AB, Pulido RS, Murphy A, Nudleman E, Daneman R, Goldberg JL (2019) Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat Commun 10(1):2477. doi: 10.1038/s41467-019-10219-8
Objective: To determine which neurons are responsible for angiogenesis and blood retinal barrier formation.
Summary: Anti-ChAT-SAP reduces SAC (starburst amacrine cell) number and inhibits deep-layer angiogenesis.
Usage: Anti-ChAT-SAP or control Rabbit-IgG-SAP were injected intravitreally at P3 and P11 (0.12 mg/mL in PBS).
Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)
Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn.
Nelson TS, Fu W, Donahue RR, Corder GF, Hökfelt T, Wiley RG, Taylor BK (2019) Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248. doi: 10.1038/s41598-019-43493-z PMID: 31076578
Objective: To test the relevance of the NPYY1 spinal population to the development and/or maintenance of acute and neuropathic pain.
Summary: This neuroanatomical and behavioral characterization of Y1R-expressing excitatory interneurons provides compelling evidence for the development of spinally-directed Y1R agonists to reduce chronic neuropathic pain.
Usage: Selectively ablated Y1R-expressing interneurons while sparing the central terminals of primary afferents. Rats received intrathecal injections of either NPY-SAP or control Blank-SAP (1000 ng each).
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Spinal somatostatin-positive interneurons transmit chemical itch.
Fatima M, Ren X, Pan H, Slade HFE, Asmar AJ, Xiong CM, Shi A, Xiong AE, Wang L, Duan B (2019) Spinal somatostatin-positive interneurons transmit chemical itch. Pain 160(5):1166-1174. doi: 10.1097/j.pain.0000000000001499
Objective: To further study the cellular identity of spinal interneurons that contribute to itch processing.
Summary: Findings reveal a novel spinal mechanism for sensory encoding of itch perception.
Usage: Npra receptor–expressing spinal cord interneurons were ablated through intrathecal injection of Nppb-SAP (5 μg/10 μL) or control Blank-SAP in lumbar segment 3 to 4. Behavioral analyses were performed 1 week after the toxin injection.
Related Products: Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)
Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice.
Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, Blackmore EM, Rance NE (2019) Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology 160(4):803-816. doi: 10.1210/en.2018-00934
Objective: To characterize the thermoregulatory role of MnPO NK3R neurons in female mice.
Summary: Study suggests that KNDy neurons modulate thermosensory pathways for heat defense indirectly via a subpopulation of glutamatergic MnPO neurons that express NK3R.
Usage: Mice were bilaterally injected with 10 ng NK3-SAP in 100 nL PBS (n = 14) or blank-SAP (n = 8) in the preoptic area adjacent to the MnPO.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.
Eidson LN, Murphy AZ (2019) Inflammatory mediators of opioid tolerance: Implications for dependency and addiction. Peptides 115:51-58. doi: 10.1016/j.peptides.2019.01.003
Objective: To determine what mediates opioid tolerance and alterations in glutamate homeostasis.
Summary: Site-specific lesions of PAG MOR-containing neurons using Dermorphin-SAP significantly reduce the antinociceptive effects of systemic morphine suggesting that PAG MOR is critical for morphine action.
Usage: Rats were injected with 3 pmol of Dermorphin-SAP (Cat. #IT-12) into the PAG. Blank-SAP (Cat. #IT-21) was used as a control.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)
Tac1-expressing neurons in the periaqueductal gray facilitate the itch-scratching cycle via descending regulation
Gao ZR, Chen WZ, Liu MZ, Chen XJ, Wan L, Zhang XY, Yuan L, Lin JK, Wang M, Zhou L, Xu XH, Sun YG (2019) Tac1-expressing neurons in the periaqueductal gray facilitate the itch-scratching cycle via descending regulation. Neuron 101(1):45-59.e9. doi: 10.1016/j.neuron.2018.11.010
Objective: To determine the neural mechanism promoting the itch-scratching cycle.
Summary: Ablation of Tac1+ but not SST+ neurons decreases itch-induced scratching behavior. l/vlPAG Tac1+ neurons Induce Scratching Behavior via a Descending Pathway.
Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Control Blank-SAP (400 ng/5 mL).
Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)
Evidence that the LH surge in ewes involves both neurokinin B-dependent and -independent actions of kisspeptin
Goodman RL, Lopez JA, Bedenbaugh MN, Connors JM, Hardy SL< Hileman SM, Coolen LM, Lehman MN (2018) Evidence that the LH surge in ewes involves both neurokinin B-dependent and -independent actions of kisspeptin. Neuroscience 2018 Abstracts 773.20 / YY14. Society for Neuroscience, San Diego, CA.
Summary: It is generally recognized that kisspeptin plays a key role in induction of the LH surge in sheep and we have reported evidence that neurokinin B (NKB) does so as well. Specifically, disrupting NKB signaling in the retrochiasmatic area (RCh) using either an antagonist to its receptor, NK3R, or lesions of NK3R-containing neurons in the RCh with a saporin conjugate (NK3-SAP) reduced the amplitude of the estrogen-induced LH surge by 50%. Because a KISS1R antagonist (p271) also produced a 50% decrease in surge amplitude, we hypothesized that these two systems are organized in series with NKB actions in the RCh stimulating kisspeptin release. If this is the case, then the combination of NK3R lesions and a KISS1R antagonist should produce the same inhibition as either treatment alone. This experiment tested this prediction using a 2 x 2 design. Breeding season ewes were ovariectomized and immediately given an estradiol (E) implant sc and two progesterone implants (CIDRs) intravaginally that produced luteal phase levels of these steroids. Ewes then received bilateral injections of either NK3-SAP (n=6) or Blank-SAP (n=5) into the RCh. Three weeks later, an artificial follicular phase was produced by inserting four 3 cm long E implants 24 hrs after CIDR removal and either saline or p271 was infused into the lateral ventricle for 16-24 hrs after E implantation; LH was monitored every 2-4 hrs for two days. CIDRs were then reinserted and the protocol repeated in a cross-over design so that all ewes received saline and p271 treatment. In Blank-SAP ewes, p271 decreased the peak of the LH surge from 61.2 ± 7.6 to 27.4 ± 4.6 ng/mL and delayed it 8 hrs (from 26.5 ± 0.5 to 34.1 ± 1.2 hrs post E implantation). The NK3-SAP injections alone decreased the peak of the LH surge to 29.7 ± 10.7 ng/mL compared to Blank-SAP, but the peak was not further inhibited by p271 in these NK3-SAP-treated ewes (24.4 ± 1.4 ng/mL). However, p271 delayed the peak of the LH surge (from 28.8 ± 1.2 to 34.8 ± 2.1 hrs post E implantation) in the ewes injected with NK3-SAP. Based on these results, we propose that kisspeptin has two roles in the LH surge in ewes: it initiates the surge independent of NKB signaling in the RCh, and maintains LH secretion during the surge by a NKB-dependent system.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21), Custom Conjugates
Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice.
Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ (2019) Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice. Mol Neurobiol 56(7):4639-4652. doi: 10.1007/s12035-018-1404-2
Objective: To investigate the contribution of CBF neuronal p75NTR to the progression of Alzheimer’s Disease
Summary: Data indicate that a direct interaction between CBF-expressed p75NTR and Aβ does not contribute significantly to the regulation of Aβ load.
Usage: To lesion CBF neurons, a single infusion of mu p75-SAP or control Rabbit IgG-SAP (0.4 mg/ml) was stereotaxically-injected into the basal forebrain.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)