Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/100615
Title: Resilience to stress and sex-specific remodeling of microglia and neuronal morphology in a rat model of anxiety and anhedonia
Authors: Gaspar, Rita 
Soares-Cunha, Carina
Domingues, Ana Verónica
Coimbra, Bárbara
Baptista, Filipa I. 
Pinto, Luísa 
Ambrósio, António 
Rodrigues, Ana João 
Gomes, Catarina A. 
Keywords: Chronic stress; Dorsal hippocampus; Microglia morphology; Nucleus accumbens; Prenatal stress; Sex
Issue Date: May-2021
Project: FCT grant (PD/BD/114116/2015) 
FCT (CEECIND/03887/2017) 
FCT (CEECIND/00922/2018) 
REWSTRESS project (PTDC/MED-NEU/29071/2017). 
FCT grant (SFRH/BD/147066/2019) 
Bial Foundation 30/2016 
POCI-01-0145-FEDER-016428 (MEDPERSYST) 
PTDC/MED-NEU/29071/2017 (REWSTRESS) 
FCT - UID/NEU/04539/2019 
UIDB/50026/2020 
UIDP/50026/2020 
UIDB/04539/2020 
UIDP/04539/2020 (CIBB) 
NORTE-01-0145-FEDER-000013 
NORTE-01-0145-FEDER-000023 
POCI-01-0145-FEDER-007440 
CENTRO-01-0145-FEDER-000008: BRAINHEALTH 2020 
Serial title, monograph or event: Neurobiology of Stress
Volume: 14
Abstract: Prenatal exposure to stress or glucocorticoids (GC) is associated with the appearance of psychiatric diseases later in life. Microglia, the immune cells of the brain, are altered in stress-related disorders. Synthetic GC such as dexamethasone (DEX) are commonly prescribed in case of preterm risk labour in order to promote fetal lung maturation. Recently, we reported long-lasting differences in microglia morphology in a model of in utero exposure to DEX (iuDEX), that presents an anxious phenotype. However, it is still unclear if stress differentially affects iuDEX males and females. In this work, we evaluated how iuDEX animals of both sexes cope with chronic mild stress for 2 weeks. We evaluated emotional behavior and microglia and neuronal morphology in the dorsal hippocampus (dHIP) and nucleus accumbens (NAc), two brain regions involved in emotion-related disorders. We report that males and females prenatally exposed to DEX have better performance in anxiety- and depression-related behavioral tests after chronic stress exposure in adulthood than non-exposed animals. Interestingly, iuDEX animals present sex-dependent changes in microglia morphology in the dHIP (hypertrophy in females) and in the NAc (atrophy in females and hypertrophy in males). After chronic stress, these cells undergo sex-specific morphological remodeling. Paralleled to these alterations in cytoarchitecture of microglia, we report inter-regional differences in dendritic morphology in a sex-specific manner. iuDEX females present fewer complex neurons in the NAc, whereas iuDEX males presented less complex neuronal morphology in the dHIP. Interestingly, these alterations were modified by stress exposure. Our work shows that stressful events during pregnancy can exert a preserved sex-specific effect in adulthood. Although the role of the observed cellular remodeling is still unknown, sex-specific differences in microglia plasticity induced by long-term stress exposure may anticipate differences in drug efficacy in the context of stress-induced anxiety- or depression-related behaviors.
URI: http://hdl.handle.net/10316/100615
ISSN: 2352-2895
DOI: 33614864
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10.1016/j.ynstr.2021.100302
33614864
Rights: openAccess
Appears in Collections:I&D ICBR - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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