TY - JOUR
T1 - The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response
AU - Dedic, Nina
AU - Chen, Alon
AU - Deussing, Jan M.
N1 - A.C. is the head of the Max Planck Society - Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics. His work is supported by: an FP7 Grant from the European Research Council (260463); Research Grant from the Israel Science Foundation (803/11); a Research support from Roberto and Renata Ruhman; Nella and Leon Benoziyo Center for Neurological Diseases; the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Perlmaan Family Foundation, Founded by Louis L. and Anita M. Perlman; the Adelis Foundation and the Irving I. Moskowitz Foundation; I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant No 1916/12). J.D.´s work has been supported by the German Federal Ministry of Education and Research within the framework of the e:Med research and funding concept (IntegraMent: Integrated Understanding of Causes and Mechanisms in Mental Disorders; FKZ 01ZX1314H), by the program for medical genome research within the framework of NGFN-Plus (FKZ: 01GS08151 and FKZ: 01GS08155), by the Max Planck Institute for Psychiatry and the Helmholtz Zentrum München with their Clinical Cooperation Group (CCG), and by the Initiative and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Health in an Ageing Society (HA-215).
PY - 2018
Y1 - 2018
N2 - Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2.Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacological studies to genetic mouse models and virus-mediated manipulations.Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, including anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiology and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions.Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mechanisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely understood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses.
AB - Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2.Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacological studies to genetic mouse models and virus-mediated manipulations.Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, including anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiology and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions.Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mechanisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely understood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses.
U2 - https://doi.org/10.2174/1874467210666170302104053
DO - https://doi.org/10.2174/1874467210666170302104053
M3 - مقالة مرجعية
SN - 1874-4672
VL - 11
SP - 4
EP - 31
JO - Current Molecular Pharmacology
JF - Current Molecular Pharmacology
IS - 1
ER -