Linked Life Data

17293846

Source:http://linkedlifedata.com/resource/pubmed/id/17293846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-7-24
pubmed:abstractText
Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1476-95
pubmed:meshHeading
pubmed-meshheading:17293846-Alkaline Phosphatase, pubmed-meshheading:17293846-Animals, pubmed-meshheading:17293846-Behavior, Animal, pubmed-meshheading:17293846-Brain, pubmed-meshheading:17293846-Cerebrovascular Circulation, pubmed-meshheading:17293846-Corticotropin-Releasing Hormone, pubmed-meshheading:17293846-Gene Expression Profiling, pubmed-meshheading:17293846-Gene Expression Regulation, pubmed-meshheading:17293846-Glucocorticoids, pubmed-meshheading:17293846-Hypothalamo-Hypophyseal System, pubmed-meshheading:17293846-In Situ Hybridization, pubmed-meshheading:17293846-Male, pubmed-meshheading:17293846-Mice, pubmed-meshheading:17293846-Mice, Knockout, pubmed-meshheading:17293846-Microcirculation, pubmed-meshheading:17293846-Molecular Sequence Data, pubmed-meshheading:17293846-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17293846-Pituitary-Adrenal System, pubmed-meshheading:17293846-Receptors, Corticotropin-Releasing Hormone, pubmed-meshheading:17293846-Reproducibility of Results, pubmed-meshheading:17293846-Signal Transduction
pubmed:year
2007
pubmed:articleTitle
Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.
pubmed:affiliation
Max Planck Institute of Psychiatry, Munich, Germany. deussing@mpipsykl.mpg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't