(Taken directly from the application). Corticotropin- driving pituitary-adrenal responses to stress. CRF is also widely pituitary-adrenal responses to stress. CRF is also widely expressed in complementary autonomic and behavioral mechanisms that are commonly invoked autonomic and behavioral mechanisms that are commonly invoked following of a functional CRF receptor (CRF-R) provides a critical tool with which to a functional CRF receptor (CRF-R) provides a critical tool with which distribution in pituitary is fully compatible with the major neuroendocrine distribution in pituitary is fully compatible with the major containing projections, particularly in regions implicated as stress- of CRF-containing projections particularly in regions implicated as identifying, and providing a functional anatomical context, for areas in aimed at identifying and providing a functional anatomical context for alternative hypotheses as to how discrepancies may be reconciled in regions to pursue alternative hypotheses as to how discrepancies may be and electron microscopic level to characterize the cellular and subcellular will be used at the light and electron microscopic level to characterize corticotropin in pituitary. Dual staining approaches will assess those of CRF in brain and of corticotropin in pituitary. Dual staining apposed to postsynaptic membrane specializations with which CRF-R-ir is terminals may be synaptically apposed to postsynaptic membrane of mRNA and/or protein expression will be employed to determine first how regions of interest. Various in situ assays of mRNA and/or protein environment, the major factors modulating CRF expression within and beyond stress and perturbations in the corticosteroid environment the major processed in CRF target cells in brain and pituitary that do and do not hypothalamus. The manner in which CRF-R is sequestered and processed in will be explored at the light and electron microscopic levels under basal another high-affinity CRF-binding moiety the CRF- binding protein will hybridization histochemical approaches like those just described to challenged conditions. Finally we will employ immuno- and hybridization accommodated by novel ligands for the CRF-R and/or the existence of major areas of apparent ligand-receptor mismatch may be accommodated by processing variants or subtypes. Alterations in titers and/or extrahypothalamic CRF can lead to Cushingoid or Addisonian symptoms, to Cushingoid or Addisonian symptoms modified susceptibility to immune the etiology of affective disorders such as anorexia nervosa and major disorders such as anorexia nervosa and major depression. Collectively neuroendocrine and neurobiological contexts for signaling by CRF at neurobiological contexts for signaling by CRF at multiple levels of stress-related neuronal and neuroendocrine systems.

Project Start
1998-06-25
Project End
1999-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
19
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Spierling, Samantha R; Mattock, Maegan; Zorrilla, Eric P (2017) Modeling hypohedonia following repeated social defeat: Individual vulnerability and dopaminergic involvement. Physiol Behav 177:99-106
Erchegyi, Judit; Wang, Lixin; Gulyas, Jozsef et al. (2016) Characterization of Multisubstituted Corticotropin Releasing Factor (CRF) Peptide Antagonists (Astressins). J Med Chem 59:854-66
Pilbrow, Anna P; Lewis, Kathy A; Perrin, Marilyn H et al. (2016) Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing. Endocrinology 157:4865-4874
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2016) Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease. Alzheimers Dement 12:527-37
Cui, Changhai; Noronha, Antonio; Warren, Kenneth R et al. (2015) Brain pathways to recovery from alcohol dependence. Alcohol 49:435-52
Perrin, Marilyn H; Tan, Laura A; Vaughan, Joan M et al. (2015) Characterization of a Pachymedusa dacnicolor-Sauvagine analog as a new high-affinity radioligand for corticotropin-releasing factor receptor studies. J Pharmacol Exp Ther 353:307-17
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2015) Corticotropin-Releasing Factor Receptor-1 Antagonism Reduces Oxidative Damage in an Alzheimer’s Disease Transgenic Mouse Model. J Alzheimers Dis 45:639-50
van der Meulen, Talitha; Huising, Mark O (2015) Role of transcription factors in the transdifferentiation of pancreatic islet cells. J Mol Endocrinol 54:R103-17
Radley, Jason J; Sawchenko, Paul E (2015) Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic-pituitary-adrenal axis adaptations to repeated stress. J Comp Neurol 523:2769-87
van der Meulen, Talitha; Donaldson, Cynthia J; Cáceres, Elena et al. (2015) Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat Med 21:769-76

Showing the most recent 10 out of 382 publications