---
_id: '9953'
abstract:
- lang: eng
  text: 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.
acknowledgement: We acknowledge that Université Laval stands on the traditional and
  unceded land of the Huron-Wendat peoples; and that the University of Victoria exists
  on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ
  peoples have relationships to this land. We thank Emmanuel Planel for the access
  to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging
  Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank
  the Centre for Advanced Materials and Related Technology for the access to the confocal
  microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds
  de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU
  de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from
  Fondation Famille-Choquette. K.B. was supported by excellence scholarships from
  Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC
  fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S.
  were supported by postdoctoral fellowships from FRQS. This study was funded by a
  Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant
  (RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T.
  and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B,
  by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier
  II Canada Research Chair in Neurobiology of Aging and Cognition.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine
  full_name: Picard, Katherine
  last_name: Picard
- first_name: Kanchan
  full_name: Bisht, Kanchan
  last_name: Bisht
- first_name: Silvia
  full_name: Poggini, Silvia
  last_name: Poggini
- first_name: Stefano
  full_name: Garofalo, Stefano
  last_name: Garofalo
- first_name: Maria Teresa
  full_name: Golia, Maria Teresa
  last_name: Golia
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Fatima
  full_name: Abdallah, Fatima
  last_name: Abdallah
- first_name: Naomi
  full_name: Ciano Albanese, Naomi
  last_name: Ciano Albanese
- first_name: Irmgard
  full_name: Amrein, Irmgard
  last_name: Amrein
- first_name: Nathalie
  full_name: Vernoux, Nathalie
  last_name: Vernoux
- first_name: Kaushik
  full_name: Sharma, Kaushik
  last_name: Sharma
- first_name: Chin Wai
  full_name: Hui, Chin Wai
  last_name: Hui
- first_name: Julie
  full_name: C. Savage, Julie
  last_name: C. Savage
- first_name: Cristina
  full_name: Limatola, Cristina
  last_name: Limatola
- first_name: Davide
  full_name: Ragozzino, Davide
  last_name: Ragozzino
- first_name: Laura
  full_name: Maggi, Laura
  last_name: Maggi
- first_name: Igor
  full_name: Branchi, Igor
  last_name: Branchi
- first_name: Marie Ève
  full_name: Tremblay, Marie Ève
  last_name: Tremblay
citation:
  ama: Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion
    alters the response of hippocampal microglia and neurons in a chronic unpredictable
    mild stress paradigm in female mice. <i>Brain, Behavior, and Immunity</i>. 2021;97:423-439.
    doi:<a href="https://doi.org/10.1016/j.bbi.2021.07.022">10.1016/j.bbi.2021.07.022</a>
  apa: Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B.,
    … Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters
    the response of hippocampal microglia and neurons in a chronic unpredictable mild
    stress paradigm in female mice. <i>Brain, Behavior, and Immunity</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.bbi.2021.07.022">https://doi.org/10.1016/j.bbi.2021.07.022</a>
  chicago: Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria
    Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid
    Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in
    a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” <i>Brain, Behavior,
    and Immunity</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.bbi.2021.07.022">https://doi.org/10.1016/j.bbi.2021.07.022</a>.
  ieee: K. Picard <i>et al.</i>, “Microglial-glucocorticoid receptor depletion alters
    the response of hippocampal microglia and neurons in a chronic unpredictable mild
    stress paradigm in female mice,” <i>Brain, Behavior, and Immunity</i>, vol. 97.
    Elsevier, pp. 423–439, 2021.
  ista: Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F,
    Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola
    C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid
    receptor depletion alters the response of hippocampal microglia and neurons in
    a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior,
    and Immunity. 97, 423–439.
  mla: Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters
    the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild
    Stress Paradigm in Female Mice.” <i>Brain, Behavior, and Immunity</i>, vol. 97,
    Elsevier, 2021, pp. 423–39, doi:<a href="https://doi.org/10.1016/j.bbi.2021.07.022">10.1016/j.bbi.2021.07.022</a>.
  short: K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F.
    Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C.
    Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain,
    Behavior, and Immunity 97 (2021) 423–439.
date_created: 2021-08-22T22:01:21Z
date_published: 2021-10-01T00:00:00Z
date_updated: 2023-10-03T09:49:18Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.bbi.2021.07.022
external_id:
  isi:
  - '000702878400007'
  pmid:
  - '34343616'
intvolume: '        97'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf
month: '10'
oa: 1
oa_version: Submitted Version
page: 423-439
pmid: 1
publication: Brain, Behavior, and Immunity
publication_identifier:
  issn:
  - 0889-1591
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglial-glucocorticoid receptor depletion alters the response of hippocampal
  microglia and neurons in a chronic unpredictable mild stress paradigm in female
  mice
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 97
year: '2021'
...