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      Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

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          Abstract

          Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

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          Most cited references313

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          Searching for a baseline: functional imaging and the resting human brain.

          Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.
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            Metabotropic glutamate receptors: physiology, pharmacology, and disease.

            The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
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              Epidemiology of women and depression.

              R Kessler (2003)
              Depression is the leading cause of disease-related disability among women in the world today. Depression is much more common among women than men, with female/male risk ratios roughly 2:1. Recent epidemiological research is reviewed. Implications are suggested for needed future research. The higher prevalence of depression among women than men is due to higher risk of first onset, not to differential persistence or recurrence. Although the gender difference first emerges in puberty, other experiences related to changes in sex hormones (pregnancy, menopause, use of oral contraceptives, and use of hormone replacement therapy) do not significantly influence major depression. These observations suggest that the key to understanding the higher rates of depression among women than men lies in an investigation of the joint effects of biological vulnerabilities and environmental provoking experiences. Advancing understanding of female depression will require future epidemiologic research to focus on first onsets and to follow incident cohorts of young people through the pubertal transition into young adulthood with fine-grained measures of both sex hormones and gender-related environmental experiences. Experimental interventions aimed at primary prevention by jointly manipulating putative biological and environmental risk factors will likely be needed to adjudicate between contending causal hypotheses regarding the separate and joint effects of interrelated risk factors.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                20 February 2015
                2015
                : 9
                : 37
                Affiliations
                [1] 1Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany
                [2] 2Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany
                [3] 3Leipzig Research Center for Civilization Diseases, University of Leipzig Leipzig, Germany
                [4] 4Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig Leipzig, Germany
                [5] 5Berlin School of Mind and Brain, Mind and Brain Institute Berlin, Germany
                Author notes

                Edited by: Belinda Pletzer, University of Salzburg, Austria

                Reviewed by: Cynthia Kuhn, Duke University Medical Center, USA; Kelly Cosgrove, Yale, USA

                *Correspondence: Julia Sacher, Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, Germany e-mail: sacher@ 123456cbs.mpg.de

                This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Neuroscience.

                Article
                10.3389/fnins.2015.00037
                4335177
                25750611
                c4ca00e4-78e4-4961-b20b-39e982a2fd39
                Copyright © 2015 Barth, Villringer and Sacher.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 August 2014
                : 26 January 2015
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 298, Pages: 20, Words: 20002
                Categories
                Endocrinology
                Review Article

                Neurosciences
                estrogens,progesterone,neurotransmitters,plasticity,hormonal transition periods
                Neurosciences
                estrogens, progesterone, neurotransmitters, plasticity, hormonal transition periods

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