Molecular Changes Induced by Stress
Gene Expression, Behavior, Endocrine and Immune Responses to Stress in Rats Induced by Corticotropin Releasing Hormone Intracerebroventricular Administration
Tech Area / Field
- MED-DRG/Drug Discovery/Medicine
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
Ministry of Education and Science of Georgia / Beritashvili Institute of Physiology, Georgia, Tbilisi
- University of Chicago, USA, IL, Chicago\nLouisiana State University / School of Medicine in Shreveport, USA, CA, Shreveport\nMunich University Clinic, Germany, Munich\nIowa State University, USA, IA, Ames\nMRC Human Reproductive Science Unit, UK, Edinburgh
Project summaryThe search of biobehavioral mechanisms of stress has been advanced by the use of corticotropin-releasing hormone (CRH) injection directly into cerebroventricular system. This neurohormone produces a number of effects that are reminiscent with the stress response of behavior, neuroendocrine, and immune systems. It is possible to evaluate all these effects in an integrated whole animal model. The focus of this grant is to use CRH administration as a model of controlled stress to determine the role of central stressor (CRH imposed) on gene expression, behavior, autonomic, endocrine, and immune functions and to determine whether catecholamine-induced response, associated with stress, plays one of key roles in changes of these functions. The working hypothesis is that catecholamines – one of the end products of the activation of the stress system – are the most important mediators of the stress response in rats, causing adverse affects on behavior, endocrine, and immune responses, and that administration of the beta-adrenergic receptor antagonist, nadolol or a CRH antagonist, alpha-helical CRH 9-41, prior to stress (CRH administration) would block the stress-induced changes in behavior, autonomic, endocrine, and immune functions. Another goal is to determine the role of central stressor (CRH imposed) in gene expression in brain structures involved in the central regulation of stress response (hypothalamus, limbic zones, neocortex, pituitary). Objectives in this grant application focus on elucidating:
Objective 1. In vivo experiments to determine the effects of CRH, administered alone or in combination with its antagonist, alpha-helical CRH 9-41 or beta-adrenergic receptor antagonist, nadolol, on behavior, adrenocorticotropin releasing hormone and cortisol release, nitric oxide and tumor necrosis factor production, plasma catecholamines level, heart rate, as CRH neurons and Brain Derived Neurotrophic Factor level (stress-responsive intercellular messenger) in brain regions, involved in the central regulation of stress response (hypothalamus, limbic zones, neocortex, pituitary).
Objective 2. To determine the specific effect of CRH on immediate early gene expression (Fos) in brain structures involved in stress response (hypothalamus, limbic zones, neocortex, pituitary).
Objective 3. On the basis of results of Objective 2 experiments to study the specific changes in gene expression in certain brain structures (maximum 4-5) by Polymerase Chain Reaction (PCR) – Select cDNA substruction approach after CRH injection induced stress.
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