--- res: bibo_abstract: - Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Katherine foaf_name: Picard, Katherine foaf_surname: Picard - foaf_Person: foaf_givenName: Kanchan foaf_name: Bisht, Kanchan foaf_surname: Bisht - foaf_Person: foaf_givenName: Silvia foaf_name: Poggini, Silvia foaf_surname: Poggini - foaf_Person: foaf_givenName: Stefano foaf_name: Garofalo, Stefano foaf_surname: Garofalo - foaf_Person: foaf_givenName: Maria Teresa foaf_name: Golia, Maria Teresa foaf_surname: Golia - foaf_Person: foaf_givenName: Bernadette foaf_name: Basilico, Bernadette foaf_surname: Basilico foaf_workInfoHomepage: http://www.librecat.org/personId=36035796-5ACA-11E9-A75E-7AF2E5697425 orcid: 0000-0003-1843-3173 - foaf_Person: foaf_givenName: Fatima foaf_name: Abdallah, Fatima foaf_surname: Abdallah - foaf_Person: foaf_givenName: Naomi foaf_name: Ciano Albanese, Naomi foaf_surname: Ciano Albanese - foaf_Person: foaf_givenName: Irmgard foaf_name: Amrein, Irmgard foaf_surname: Amrein - foaf_Person: foaf_givenName: Nathalie foaf_name: Vernoux, Nathalie foaf_surname: Vernoux - foaf_Person: foaf_givenName: Kaushik foaf_name: Sharma, Kaushik foaf_surname: Sharma - foaf_Person: foaf_givenName: Chin Wai foaf_name: Hui, Chin Wai foaf_surname: Hui - foaf_Person: foaf_givenName: Julie foaf_name: C. Savage, Julie foaf_surname: C. Savage - foaf_Person: foaf_givenName: Cristina foaf_name: Limatola, Cristina foaf_surname: Limatola - foaf_Person: foaf_givenName: Davide foaf_name: Ragozzino, Davide foaf_surname: Ragozzino - foaf_Person: foaf_givenName: Laura foaf_name: Maggi, Laura foaf_surname: Maggi - foaf_Person: foaf_givenName: Igor foaf_name: Branchi, Igor foaf_surname: Branchi - foaf_Person: foaf_givenName: Marie Ève foaf_name: Tremblay, Marie Ève foaf_surname: Tremblay bibo_doi: 10.1016/j.bbi.2021.07.022 bibo_volume: 97 dct_date: 2021^xs_gYear dct_identifier: - UT:000702878400007 dct_isPartOf: - http://id.crossref.org/issn/0889-1591 dct_language: eng dct_publisher: Elsevier@ dct_title: Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice@ fabio_hasPubmedId: '34343616' ...