Expression Profiling Identifies the CRH/CRH-R1 System as a Modulator of Neurovascular Gene Activity

摘要: 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 pathways CRH/CRH-R1-dependent signaling mechanisms underlying behavioral phenotype as well consequences lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling brains CRH-R1 mutant wild-type using our custom made MPIP (Max Planck Institute Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered levels when comparing knockout with littermates. A significant proportion differentially expressed was related to control HPA hypothalamic-pituitary-thyroid (HPT) axes reflecting not only disturbance axis in but also interplay both systems. spatial regulated revealed prevalence for cerebral microvasculature. This confirmed successful cross-validation CRH overexpressing mice. Analysis vasculature alterations functional rather than structural properties. direct role CRH/CRH-R1 system supported demonstrating Crhr1 adult murine vasculature. In conclusion, these data suggest novel, previously unknown modulating neurovascular gene function.