title: The functions of estrogen receptor beta in the female brain: A systematic review.
abstract: Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERβ) has been suggested as a therapeutic target. However, little is known about the role of ERβ in the female brain. Six electronic databases were searched for articles evaluating the role of ERβ in the female brain and the influence of age and menopause on ERβ function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERβ phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERβ may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERβ, future studies should be conducted in humans to further our understanding of the importance of ERβ in women's mental and cognitive health.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Kris G
authors.initials: KG
authors.lastname: Vargas
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jelena
authors.initials: J
authors.lastname: Milic
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Asija
authors.initials: A
authors.lastname: Zaciragic
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Wen
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Loes
authors.initials: L
authors.lastname: Jaspers
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jana
authors.initials: J
authors.lastname: Nano
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Klodian
authors.initials: K
authors.lastname: Dhana
authors.affiliation: Medical Library, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Wichor M
authors.initials: WM
authors.lastname: Bramer
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Biomedical Sciences, Faculty of Medicine, University of Medicine, Tirana, Albania; University Clinic of Gastrohepatology, University Hospital Center Mother Teresa, Tirana, Albania.
authors.forename: Bledar
authors.initials: B
authors.lastname: Kraja
authors.affiliation: Department of Public Health, Erasmus University Medical Center, The Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: van Beeck
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Neurology, Erasmus University Medical Center, The Netherlands; Department of Radiology, Erasmus University Medical Center, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: t.muka@erasmusmc.nl.
authors.forename: Taulant
authors.initials: T
authors.lastname: Muka
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism / Q000523:psychology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism / Q000523:psychology; D010766:Phosphorylation
chemical_list: D047629:Estrogen Receptor beta
keywords: Brain; Estrogen receptor beta; Menopause; Neurological disorders; Psychiatry; Systematic review