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Listening to mutant mice: a spotlight on the role of CRF/CRF receptor systems in affective disorders


Keck, M E; Ohl, F; Holsboer, F; Müller, M B (2005). Listening to mutant mice: a spotlight on the role of CRF/CRF receptor systems in affective disorders. Neuroscience and Biobehavioral Reviews, 29(4-5):867-889.

Abstract

Genetically engineered mice were originally generated to delineate the role of a specific gene product in behavioral or neuroendocrine phenotypes, rather than to produce classic animal models of depression. To learn more about the neurobiological mechanisms underlying a clinical condition such as depression, it has proven worthwhile to investigate changes in behaviors characteristic of depressed humans, such as anxiety, regardless of whether or not these alterations may also occur in other disorders besides depression. The majority of patients with mood and anxiety disorders have measurable shifts in their stress hormone regulation as reflected by elevated secretion of central and peripheral stress hormones or by altered hormonal responses to neuroendocrine challenge tests. In recent years, these alterations have been increasingly translated into testable hypotheses addressing the pathogenesis of illness. Refined molecular technologies and the creation of genetically engineered mice have allowed to specifically target individual genes involved in regulation of corticotropin releasing factor (CRF) system elements (e.g. CRF and CRF-related peptides, their receptors, binding protein). Studies performed in such mice have complemented and extended our knowledge. The cumulative evidence makes a strong case implicating dysfunction of these systems in the pathogenesis of depression and leads us beyond the monoaminergic synapse in search of eagerly anticipated strategies to discover and develop better therapies for depression.

Abstract

Genetically engineered mice were originally generated to delineate the role of a specific gene product in behavioral or neuroendocrine phenotypes, rather than to produce classic animal models of depression. To learn more about the neurobiological mechanisms underlying a clinical condition such as depression, it has proven worthwhile to investigate changes in behaviors characteristic of depressed humans, such as anxiety, regardless of whether or not these alterations may also occur in other disorders besides depression. The majority of patients with mood and anxiety disorders have measurable shifts in their stress hormone regulation as reflected by elevated secretion of central and peripheral stress hormones or by altered hormonal responses to neuroendocrine challenge tests. In recent years, these alterations have been increasingly translated into testable hypotheses addressing the pathogenesis of illness. Refined molecular technologies and the creation of genetically engineered mice have allowed to specifically target individual genes involved in regulation of corticotropin releasing factor (CRF) system elements (e.g. CRF and CRF-related peptides, their receptors, binding protein). Studies performed in such mice have complemented and extended our knowledge. The cumulative evidence makes a strong case implicating dysfunction of these systems in the pathogenesis of depression and leads us beyond the monoaminergic synapse in search of eagerly anticipated strategies to discover and develop better therapies for depression.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2005
Deposited On:05 Sep 2011 08:42
Last Modified:16 Aug 2016 10:14
Publisher:Elsevier
ISSN:0149-7634
Publisher DOI:https://doi.org/10.1016/j.neubiorev.2005.03.003
PubMed ID:15899517

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