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Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity

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Autor(es):
Dedic, Nina [1, 2, 3] ; Kuhne, Claudia [3] ; Gomes, Karina S. [4, 3] ; Hartmann, Jakob [1, 2, 5] ; Ressler, Kerry J. [1, 2] ; Schmidt, V, Mathias ; Deussing, Jan M. [3]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] McLean Hosp, 115 Mill St, Belmont, MA 02178 - USA
[2] Harvard Med Sch, Dept Psychiat, Belmont, MA - USA
[3] Max Planck Inst Psychiat, Mol Neurogenet, Munich - Germany
[4] Univ Estadual Paulista, Lab Neuropsychopharmacol, Araraquara - Brazil
[5] V, Max Planck Inst Psychiat, Stress Resilience, Munich - Germany
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN NEUROSCIENCE; v. 13, SEP 20 2019.
Citações Web of Science: 1
Resumo

Dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in stress-related psychopathologies such as depression and anxiety. Although most studies have linked CRH/CRH receptor 1 signaling to aversive, stress-like behavior, recent work has revealed a crucial role for distinct CRH circuits in maintaining positive emotional valence and appetitive responses under baseline conditions. Here we addressed whether deletion of CRH, specifically from GABAergic forebrain neurons (Crh(CKO-GABA) mice) differentially affects general behavior under baseline and chronic stress conditions. Expression mapping in Crh(CKO-GAB)A mice revealed absence of Crh in GABAergic neurons of the cortex and limbic regions including the hippocampus, central nucleus of the amygdala and the bed nucleus of the stria terminals, but not in the paraventricular nucleus of hypothalamus. Consequently, conditional CRH knockout animals exhibited no alterations in circadian and stress-induced corticosterone release compared to controls. Under baseline conditions, absence of Crh from forebrain GABAergic neurons resulted in social interaction deficits but had no effect on other behavioral measures including locomotion, anxiety, immobility in the forced swim test, acoustic startle response and fear conditioning. Interestingly, following exposure to chronic social defeat stress, Crh(CKO-GABA) mice displayed a resilient phenotype, which was accompanied by a dampened, stress-induced expression of immediate early genes c-fos and zif268 in several brain regions. Collectively our data reveals the requirement of GABAergic CRH circuits in maintaining appropriate social behavior in naive animals and further supports the ability of CRH to promote divergent behavioral states under baseline and severe stress conditions. (AU)

Processo FAPESP: 13/03445-3 - Efeitos da superexpressão do Fator de Liberação de Corticotropina (CRF) e nocaute de receptores Crf1 e Crf2 em regiões límbicas sobre o comportamento defensivo de camundongos: influência do estresse agudo e crônico
Beneficiário:Karina Santos Gomes
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado