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      The estrous cycle and 17β‐estradiol modulate the electrophysiological properties of rat nucleus accumbens core medium spiny neurons

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          Abstract

          The nucleus accumbens core is a key nexus within the mammalian brain for integrating the premotor and limbic systems and regulating important cognitive functions such as motivated behaviors. Nucleus accumbens core functions show sex differences and are sensitive to the presence of hormones such as 17β‐estradiol (estradiol) in normal and pathological contexts. The primary neuron type of the nucleus accumbens core, the medium spiny neuron (MSN), exhibits sex differences in both intrinsic excitability and glutamatergic excitatory synapse electrophysiological properties. Here, we provide a review of recent literature showing how estradiol modulates rat nucleus accumbens core MSN electrophysiology within the context of the estrous cycle. We review the changes in MSN electrophysiological properties across the estrous cycle and how these changes can be mimicked in response to exogenous estradiol exposure. We discuss in detail recent findings regarding how acute estradiol exposure rapidly modulates excitatory synapse properties in nucleus accumbens core but not caudate‐putamen MSNs, which mirror the natural changes seen across estrous cycle phases. These recent insights demonstrate the strong impact of sex‐specific estradiol action upon nucleus accumbens core neuron electrophysiology.

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          Sex bias in neuroscience and biomedical research.

          Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex. Copyright © 2010 Elsevier Ltd. All rights reserved.
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            Female mice liberated for inclusion in neuroscience and biomedical research.

            The underrepresentation of female mice in neuroscience and biomedical research is based on the assumption that females are intrinsically more variable than males and must be tested at each of four stages of the estrous cycle to generate reliable data. Neither belief is empirically based. In a meta-analysis of 293 articles, behavioral, morphological, physiological, and molecular traits were monitored in male mice and females tested without regard to estrous cycle stage; variability was not significantly greater in females than males for any endpoint and was substantially greater in males for several traits. Group housing of mice increased variability in both males and females by 37%. Utilization of female mice in neuroscience research does not require monitoring of the estrous cycle. The prevalence of sex differences at all levels of biological organization, and limitations in generalizing findings obtained with males to females, argue for the routine inclusion of female rodents in most research protocols. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Sex-specific transcriptional signatures in human depression

              Brain-region-specific RNA-seq from humans with major depressive disorder reveals unique transcriptomic profiles in males and females, with little overlap.
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                Author and article information

                Contributors
                jemeitze@ncsu.edu
                Journal
                J Neuroendocrinol
                J Neuroendocrinol
                10.1111/(ISSN)1365-2826
                JNE
                Journal of Neuroendocrinology
                John Wiley and Sons Inc. (Hoboken )
                0953-8194
                1365-2826
                02 April 2022
                June 2022
                : 34
                : 6 ( doiID: 10.1111/jne.v34.6 )
                : e13122
                Affiliations
                [ 1 ] Department of Biological Sciences North Carolina State University Raleigh NC USA
                [ 2 ] Neurobiology Laboratory National Institute of Environmental Health Sciences, NIH Research Triangle Park NC USA
                [ 3 ] Graduate Program for Neuroscience and Department of Biomedical Engineering Boston University Boston MA USA
                [ 4 ] Comparative Medicine Institute North Carolina State University Raleigh NC USA
                [ 5 ] Center for Human Health and the Environment North Carolina State University Raleigh NC USA
                Author notes
                [*] [* ] Correspondence

                John Meitzen, Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.

                Email: jemeitze@ 123456ncsu.edu

                Author information
                https://orcid.org/0000-0002-6332-6951
                https://orcid.org/0000-0002-8860-4110
                Article
                JNE13122
                10.1111/jne.13122
                9250601
                35365910
                39feec09-b26c-44b3-be6c-4513750ff360
                © 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 February 2022
                : 06 December 2021
                : 22 February 2022
                Page count
                Figures: 3, Tables: 0, Pages: 12, Words: 10980
                Funding
                Funded by: National Institute of Environmental Health Sciences , doi 10.13039/100000066;
                Award ID: P30ES025128
                Funded by: National Institute of Mental Health , doi 10.13039/100000025;
                Award ID: R01MH109471
                Categories
                Invited Review
                Fundamental and Mechanistic Neuroendocrinology
                Invited Review
                Custom metadata
                2.0
                June 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Endocrinology & Diabetes
                estradiol,estrogen receptors,estrous cycle,nucleus accumbens,sex differences

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