title: Adenosine A2Areceptor regulation of microglia morphological remodeling-gender bias in physiology and in a model of chronic anxiety.
abstract: Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, responsive to GCs and morphologically altered in stress-related disorders. These cells are regulated by adenosine A2Areceptors, which are also involved in the pathophysiology of anxiety. We now compare animal behavior and microglia morphology in males and females prenatally exposed to the GC dexamethasone. We report that prenatal exposure to dexamethasone is associated with a gender-specific remodeling of microglial cell processes in the prefrontal cortex: males show a hyper-ramification and increased length whereas females exhibit a decrease in the number and in the length of microglia processes. Microglial cells re-organization responded in a gender-specific manner to the chronic treatment with a selective adenosine A2Areceptor antagonist, which was able to ameliorate microglial processes alterations and anxiety behavior in males, but not in females.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Caetano
authors.affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Pinheiro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Patrício
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Mateus-Pinheiro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: N D
authors.initials: ND
authors.lastname: Alves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: B
authors.initials: B
authors.lastname: Coimbra
authors.affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.
authors.forename: F I
authors.initials: FI
authors.lastname: Baptista
authors.affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: S N
authors.initials: SN
authors.lastname: Henriques
authors.affiliation: ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: C
authors.identifier: 0000-0003-2550-6422
authors.initials: C
authors.lastname: Cunha
authors.affiliation: ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Santos
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.
authors.forename: S G
authors.initials: SG
authors.lastname: Ferreira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: V M
authors.initials: VM
authors.lastname: Sardinha
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: J F
authors.initials: JF
authors.lastname: Oliveira
authors.affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Ambrósio
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: N
authors.identifier: 0000-0002-8755-5126
authors.initials: N
authors.lastname: Sousa
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: R A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rodrigues
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: L
authors.identifier: 0000-0002-7724-0446
authors.initials: L
authors.lastname: Pinto
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI Consortium, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: C A
authors.initials: CA
authors.lastname: Gomes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001008:Anxiety Disorders / Q000473:pathology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D063507:Sexism
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D043705:Receptor, Adenosine A2A; D003907:Dexamethasone