15 entries found for : it-13
Tectal CRF R1 receptors modulate food intake.
Prater C, Harris B, Merrill A, Aliyas A, Anderson K, Carr J (2016) Tectal CRF R1 receptors modulate food intake. Neuroscience 2016 Abstracts 257.08 / DDD9. Society for Neuroscience, San Diego, CA.
Summary: The optic tectum (OT) and superior colliculus (SC) rapidly inhibit food intake when a visual threat is present. Previous work from our laboratory indicates that CRF, acting on CRF R1 receptors, may play a role in tectal inhibition of prey capture. Here we test the hypothesis that tectal CRF neurons modulate food intake in juvenile Xenopus laevis. We tested five predictions: 1) Does tectal CRF injection decrease food intake? 2) Does a selective CRF R1 antagonist block CRF effects on feeding? 3) Does a selective CRF R1 antagonist block stressor-induced inhibition of feeding? 4) Does eliminating tectal cells expressing CRF R1 increase feeding? 5) Does food deprivation increase food intake and, if so, can this be reversed with CRF? X. laevis were administered oCRF alone or in combination with the selective CRF R1 antagonist NBI27914 or antagonist vehicle. Test agents were bilaterally injected into the tecta of juvenile frogs. CRF conjugated to the ribosomal toxin saporin (CRF-SAP) was administered 2 wk prior to testing to eliminate tectal cells expressing CRF R1. oCRF administered bilaterally into the tecta significantly reduced food intake compared to sham and vehicle injected juveniles. When frogs were injected with oCRF and antagonist vehicle, food intake was significantly reduced. When injected with both NBI27914 and oCRF, food intake was maintained at baseline levels. Frogs ate significantly less when exposed to a reactive stressor (ether vapors) and when pre-treated with antagonist vehicle prior to exposure. NBI27914 reversed stressor-induced inhibition of food intake. Neither CRF-SAP injection nor food deprivation (2 wk) significantly changed food intake. No significant differences in food intake were noted between males and females across all studies. Overall, we found support for questions 1-3 and conclude that activation of the tectal CRF R1 inhibits food intake in frogs. Furthermore, tectal CRF R1 receptors appear to be involved in the reduction of food intake that occurs in response to a reactive stressor. However, elimination of tectal CRF R1 neurons did not increase feeding suggesting that this system may be more important for stress-related vs. baseline feeding. This work was done in partial completion of requirements for the doctoral degree at Texas Tech University (C.P.)
Related Products: CRF-SAP (Cat. #IT-13)
Kumar JR, Rajkumar R, Lee LC, Dawe GS (2016) Featured Article: Targeted lesioning reveals role of nucleus incertus in the anxiogenic effect of buspirone. Targeting Trends 17(4)
Related Products: CRF-SAP (Cat. #IT-13)
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Kumar J, Rajkumar R, Lee L, Dawe G (2016) Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors. Neuropharmacology 110:1-14. doi: 10.1016/j.neuropharm.2016.07.019
Summary: The nucleus incertus (NI) is involved in stress and anxiety responses. The NI is a cluster of GABAergic neurons in the brainstem, and coexpresses CRF, 5-HT1A and D2 receptors. Buspirone is a partial agonist of 5-HT1A receptors, an antagonist of D2 receptors, and activates the NI. Buspirone is an anti-anxiety drug, but preclinical studies showed that it induces anxiety at high doses. To see if the NI is necessary for the anxiogenic effects of high doses of buspirone, rats were bilaterally injected with 86 ng of CRF-SAP (Cat. #IT-13) into the NI. Blank-SAP (Cat. #IT-21) was used as a control. NI lesioning alone had an anxiogenic effect in several anxiety screening tests compared to sham-lesioned rats, which suggests that the NI reduces anxiety physiologically. Lesioning with CRF-SAP reduced the anxiogenic effects of intra-NI injections of buspirone. No significant difference in the anxiety screening tests resulted from injecting quinpiole, a D2 agonist, which suggests that the 5HT1A receptors in the NI are involved in the anxiogenic effects of buspirone.
Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)
Lee CL, Rajkumar R, Dawe GS (2014) Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus. Targeting Trends 15(2)
Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)
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Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate.
Lee LC, Rajkumar R, Dawe GS (2014) Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate. Brain Res 1543:179-190. doi: 10.1016/j.brainres.2013.11.021
Summary: In this work the authors used CRF-SAP (Cat. #IT-13) to eliminate CRF1 receptor-expressing cells from the nucleus incertus (NI). Rats received bilateral CRF-SAP injections of 21.5 to 86 ng into the NI. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed a significant loss of CRF1 receptor-expressing cells, along with a decrease in relaxin-3 and GAD65 expression.
Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)
The nucleus incertus contributes to the anxiety-like behaviour in rats
Lee C, Rajkumar R, Suri S, Chin WM, Dawe GS (2011) The nucleus incertus contributes to the anxiety-like behaviour in rats. Neuroscience 2011 Abstracts 901.09. Society for Neuroscience, Washington, DC.
Summary: The nucleus incertus (NI), the principal source of relaxin-3 (Rln3) in the brain, is found in the periventricular gray, ventral and medial to the posterodorsal tegmental nucleus (PDTg). Several neuroanatomical studies have indicated that the NI projects to putative correlates of anxiety, especially the amygdala. Relaxin family peptide receptor type-3 (Rxfp3), the native receptor for Rln3, is expressed in the amygdala. These studies have hence predicted that the NI is strategically located to control neural circuits that underlie anxiety-like behaviour in rodents. Presence of Rln3-immunoreactive nerve fibres in the amygdala suggested the involvement of the Rln3/Rxfp3 system. Corticotrophin-releasing factor receptors type-1 (Crfr-1), one of the important anxiolytic drug targets, are prominently expressed in the NI neurons. Based on the aforesaid anatomical and receptor distribution reports, the present investigation was designed to clarify the function of the NI in anxiety-like behaviour of rats. We hypothesized that lesioning of the NI and the resulting decrease in Rln3 would affect the regulation of stress and anxiety response in rats. Firstly, the effect of NI neuron ablation, by CRF-Saporin toxin, on fear conditioning and elevated plus maze (EPM) exploration paradigms was evaluated. Secondly, the firing rates of NI neurons as the rat explored the EPM were assessed. Lastly, the effects of high frequency simulation of the NI on the expression of immediate early genes (IEG) in the amygdala were studied. The results revealed that, in a cued fear conditioning paradigm, NI-lesioned rats exhibited greater fear, indicated by longer freezing periods in the test phase, than sham-lesioned rats. Likewise, in the EPM, NI-lesioned rats made fewer entries into and spent less time in the open arms demonstrating an anxious phenotype. In addition, the NI also showed distinct firing patterns in the open and closed arms of the EPM. Stimulation of the NI activated the medial amygdaloid (MeA) nucleus as indicated by the increased expression of markers of neuronal activation. To sum up, the present study shows a significant contribution of the NI and NI-MeA pathway in the anxiety-like behaviour of rats. It also suggests that the NI and/or Rln3 have a role in the regulation of anxiety-like behaviour, implicating them as targets for anxiety-related disorders.
Related Products: CRF-SAP (Cat. #IT-13)
Targeting inhibitory neurons in the superficial dorsal horn: Somatostatin-saporin
Chatterjee K, Lemons LL, Wiley RG (2010) Targeting inhibitory neurons in the superficial dorsal horn: Somatostatin-saporin. Neuroscience 2010 Abstracts 585.1/XX15. Society for Neuroscience, San Diego, CA.
Summary: Intrathecal injection of somatostatin (SST), or the long-acting congener, octreotide, have been reported analgesic in humans with intractable pain. The principal SST receptor, sst2a, is expressed by GABAergic neurons in the superficial dorsal horn of the spinal cord. In the present study, we sought to determine the nocifensive behavioral effects of selectively destroying sst2a-expressing dorsal horn neurons using intrathecal injection of the targeted toxin, SST-saporin. SST-sap (500-625 ng) was injected intrathecally into rats followed by thermal plate and thermal preference shuttle box testing for up to three weeks. One of three rats injected with 625 ng of SST-sap developed severe persistent scratching of its lower body. Compared to vehicle controls and rats injected with 500 ng of corticotrophin releasing factor (CRF)-saporin, the SST-sap rats showed initially prolonged latencies and decreased nocifensive reflex responses on the 44 C hotplate that persisted for up to 17 days before returning to control levels. SST-sap rats also showed decreased reflex responses on the 0.3 C cold plate. Lastly, SST-sap rats showed no change in thermal preference in a shuttle box with floor temperatures of 15 C vs 45 C. CRF-sap rats showed delayed onset (after 8 days) of decreased hotplate responding and increased hot side occupancy in the thermal preference shuttle box. These results suggest, at the doses used, that SST-sap produced incomplete depletion of target neurons followed by compensatory plasticity, whereas, CRF-sap produced no primary effect but induced secondary plasticity resulting in long term decrease in responses to aversive heat. Higher dose studies and anatomic analysis of lesions produced by these agents are planned.
Related Products: CRF-SAP (Cat. #IT-13)
Pain is a salient “stressor” that is mediated by corticotropin-releasing factor-1 receptors.
Hummel M, Cummons T, Lu P, Mark L, Harrison JE, Kennedy JD, Whiteside GT (2010) Pain is a salient "stressor" that is mediated by corticotropin-releasing factor-1 receptors. Neuropharmacology 59(3):160-166. doi: 10.1016/j.neuropharm.2010.05.001
Summary: Given that corticotrophin-releasing factor (CRF) plays a major role in the response to stress, the authors investigated the role CRF-1 receptors may play in the perception of pain. Both rats and mice received 10µl intrathecal injections of 10 µM CRF-SAP (Cat. #IT-13) following a spinal nerve ligation. Administration of CRF-SAP attenuated tactile hypersensitivity, indicating that CRF-1 receptors are involved in pain perception.
Related Products: CRF-SAP (Cat. #IT-13)
Pascual J, Heinrichs SC (2007) Olfactory neophobia and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin releasing factor. Epilepsia 48:827-833. doi: 10.1111/j.1528-1167.2007.01024.x
Summary: Olfactory recognition has been linked to epilepsy in behavioral phenotype models. This work examines the role brain stress neuropeptides play in the manifestation of neurological perturbations. Mice were injected with 2 µg/5 µl of CRF-SAP (Cat. #IT-13) into the lateral ventricle. Saporin (Cat. #PR-01) was used as a control. The lesioned mice displayed a temporary reduction in seizure susceptibility, and the reversal of olfactory deficits towards the detection of food.
Related Products: CRF-SAP (Cat. #IT-13), Saporin (Cat. #PR-01)
Turner LH, Lim CE, Heinrichs SC (2007) Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor. Epilepsy Behav 10(1):8-15. doi: 10.1016/j.yebeh.2006.08.013
Summary: There appears to be an inverse relationship between seizure susceptibility and social interaction. This work examines the role that CRF may play in this system. 2.5 µg of CRF-SAP (Cat. #IT-13) was administered to the lateral ventricle of rats, and the lesioned animals were assessed in terms of social investigation times as well as handling-induced seizures. The results support the involvement of CRF systems in facilitating evoked seizures and suppression of social activity.
Related Products: CRF-SAP (Cat. #IT-13)
Possible role of CRF peptides in burn-induced hypermetabolism.
Chance WT, Dayal R, Friend LA, Sheriff S (2006) Possible role of CRF peptides in burn-induced hypermetabolism. Life Sci 78(7):694-703. doi: 10.1016/j.lfs.2005.05.083
Summary: Burn trauma has been associated with hypermetabolism and anorexia. Corticotropin releasing factor (CRF) elevates metabolic rate and elicits anorexia, while neuropeptide Y (NPY) reduces metabolic rate while stimulating feeding. After burn treatment, rats were injected with 2.5 µg CRF-SAP (Cat. #IT-13) into the third ventricle. Several parameters, including resting energy expenditure, NPY concentrations in the paraventricular nucleus, and CRFr-2 density were evaluated post-treatment. The results indicate that the CRFr-2 is important in maintaining hypermetabolism resulting from burn trauma.
Related Products: CRF-SAP (Cat. #IT-13)
Chance WT, Dayal R, Friend L, Sheriff S (2004) Intraventricular injection of CRF receptor 2 antisense oligonucleotide reduces burn-induced hypermetabolism. Neuroscience 2004 Abstracts 890.22. Society for Neuroscience, San Diego, CA.
Summary: Following major burn trauma, mammals exhibit a prolonged hypermetabolic response proportional to the size of the burn. The ability to control metabolic rate would likely result in better clinical management of burn patients. Our research employing a saporin-CRF conjugate to lesion CRF receptors suggested that activity at CRF receptor(R)-2 mediated increased resting energy expenditure (REE) in burned rats. In the present study we assessed whether treatment of burned rats with antisense oligonucleotides (ON) to CRF or CRF R-2 would reduce REE. Following anesthetization (ketamine/xylazine:80/15 mg/kg,), cannulae (24 ga) were implanted into the 3rd ventricle of 52 adult, male, SD rats. Two weeks later, these rats were anesthetized and subjected to a 25 sec, 30% body surface area, open flame burn (n = 30) or sham burn procedures (n = 22). Following (2-6 days) the burn trauma, either sense or antisense ONs to CRF (15 ug) or CRF R-2 (20 ug) was injected, ivt. REE (kcal/kg/24 hrs) was determined in these rats 7 and 14 days after burn by indirect calorimetry. Treatment with CRF antisense ON did not reduce REE in any groups. Burned rats given the CRF R-2 sense ON exhibited significant hypermetabolism both 7 (188±5 vs 156± 9) and 14 (201±8 vs 151±14) days post-burn, as compared to sham-burned rats. Burned rats treated with the CRF R-2 antisense ON were not significantly different from sham burned rats 7 (169±8) or 14 (167±5) days post-burn. Since the antisense treatment should decrease translation of message into protein at the receptor, these results suggest that activity at the CRF-2 receptor is necessary for expression of burn-induced hypermetabolism. Therefore, it is possible that CRF-2 receptor antagonists could be useful in treating burn-induced hypermetabolism.
Related Products: CRF-SAP (Cat. #IT-13)
Wiley RG, Lappi DA (2003) Targeted toxins in pain. Adv Drug Deliv Rev 55(8):1043-1054. doi: 10.1016/s0169-409x(03)00102-9
Summary: The authors discuss the use of 'molecular neurosurgery' in the study of nociception. Applications using targeted toxins, which include immunotoxins, protein-toxin conjugates, or peptide-toxin conjugates, are illustrated. The authors describe the use of these molecules as research tools, as well as their potential for therapeutics. A helpful table is included that lists neuronal surface markers and class of cells targeted for each targeted toxin. Reagents discussed: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-Saporin (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP (Cat. #IT-12), Orexin-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), and acetylated LDL-SAP (Cat. #IT-08).
Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Orexin-B-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), Acetylated LDL-SAP (Cat. #IT-08)
Fox K, Wolff I, Curtis A, Pernar L, Van Bockstaele EJ, Valentino RJ (2002) Multiple lines of evidence for the existence of corticotropin-releasing factor (CRF) receptors on locus coeruleus (LC) neurons. Neuroscience 2002 Abstracts 637.9. Society for Neuroscience, Orlando, FL.
Summary: Several physiological and anatomical findings suggest that CRF acts as a neuromodulator of LC neuronal activity. However, in situ hybridization studies have failed to demonstrate the existence of CRF receptor mRNA in LC neurons, arguing against a direct effect on these neurons. Here, a combination of techniques was used to test the hypothesis that LC neurons express CRF receptors. Primers for CRF-R1 and beta-actin were generated and micropunches of the LC were subjected to RT-PCR analysis. Bands at the predicted size for each PCR product were detected in samples obtained from the LC. The presence of CRF-receptor immunolabeling in LC tissue was also examined in Western blots. This revealed a band at 52 kD, consistent with the molecular weight reported in brain and the band was absent in membranes incubated with a combination of the CRF receptor antisera and the blocking peptide. In dual labeling immunohistochemical studies, tyrosine hydroxylase (TH) immunolabeled LC neurons exhibited CRF-receptor immunolabeling and this was absent in sections that were incubated in antisera that was preabsorbed with the blocking peptide. Ultrastructural analysis also revealed co-localization of CRF-receptor immunolabeling and TH in LC dendrites. Finally, intra-LC injection of a CRF-saporin conjugate (40-60 ng in 30 nl), but not unconjugated saporin, resulted in a time dependent neuronal damage that was selective to LC neurons. The present findings provide convergent evidence for the existence of CRF receptors in LC neurons.
Related Products: CRF-SAP (Cat. #IT-13)
Maciejewski-Lenoir D, Heinrichs SC, Liu X-J, Ling N, Tucker A, Xie Q, Lappi DA, Grigoriadis DE (2000) Selective impairment of corticotropin-releasing factor1 (CRF1) receptor-mediated function using CRF coupled to saporin. Endocrinol 141:498-504. doi: 10.1210/endo.141.2.7336
Summary: Corticotropin-releasing factor 1 (CRF1) is a 41-amino acid peptide which mediates many of the body's behavioral, autonomic, immune, and endocrine responses to stress. Reduced activation of the CRF systems plays a role in a variety of psychiatric and metabolic disease states. Maciejewski-Lenoir et al. have developed a CRF-SAP targeted toxin that can eliminate cells expressing the CRF1 but not CRF2a receptors. These data indicate that CRF-SAP (Cat. #IT-13) may be useful as a tool to examine receptor-selective impairment of CRF system function.
Related Products: CRF-SAP (Cat. #IT-13)