Biology of Sex Differences最新文献

{"title":"Sex differences in mitochondrial gene expression during viral myocarditis.","authors":"Damian N Di Florio, Gabriel J Weigel, David J Gorelov, Elizabeth J McCabe, Danielle J Beetler, Katie A Shapiro, Katelyn A Bruno, Isha Chekuri, Angita Jain, Emily R Whelan, Gary R Salomon, Sami Khatib, Natalie E Bonvie-Hill, Jessica J Fliess, Presley G Giresi, Charwan Hamilton, Cameron J Hartmoyer, Varsini Balamurugan, Ashley A Darakjian, Brandy H Edenfield, S Christian Kocsis, Christopher J McLeod, Leslie T Cooper, Étienne Audet-Walsh, Michael J Coronado, Jon Sin, DeLisa Fairweather","doi":"10.1186/s13293-024-00678-0","DOIUrl":"https://doi.org/10.1186/s13293-024-00678-0","url":null,"abstract":"<p><strong>Background: </strong>Myocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood.</p><p><strong>Methods: </strong>Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis.</p><p><strong>Results: </strong>As expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis.</p><p><strong>Conclusions: </strong>Females with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"104"},"PeriodicalIF":4.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differentially affects pro-inflammatory cell subsets in adipose tissue depots in a diet induced obesity model.","authors":"Lisa T Schuetz, Gayel Duran, Paulien Baeten, Daphne Lintsen, Doryssa Hermans, Sarah Chenine, Janne Verreycken, Tim Vanmierlo, Kristiaan Wouters, Bieke Broux","doi":"10.1186/s13293-024-00677-1","DOIUrl":"https://doi.org/10.1186/s13293-024-00677-1","url":null,"abstract":"<p><p>Obesity is a growing pandemic that increases the risk for cardiovascular diseases, type 2 diabetes, and particularly in women also the risk of cancer and neurodegenerative disorders such as dementia and multiple sclerosis. Preclinical studies on obesity focus on male mice as they gain bodyweight faster and show a clear pro-inflammatory phenotype. Here, using male and female mice, we induced obesity by feeding a high fat diet (HFD), and compared adipose tissue (AT) inflammation at the same adiposity stage (% AT/bodyweight) between both sexes. Doing so, we identified that female mice show an increase in the number of pro-inflammatory immune cells in the visceral AT at a lower adiposity stage than male mice, but the effect of HFD is diminished with higher adiposity. Interestingly, only female mice showed an increase in immune cells in the subcutaneous AT after HFD feeding. Nonetheless, we found that pro-inflammatory cytokines in blood plasma mirror the inflammatory stage of the visceral AT in both male and female mice. Uniquely in male mice, myeloid cells in the visceral AT showed a higher inflammasome activation upon HFD. In summary, we showed that adiposity differentially affects immune cells in fat depots based on sex.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"105"},"PeriodicalIF":4.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice.","authors":"Timothy M Griffin, Erika Barboza Prado Lopes, Dominic Cortassa, Albert Batushansky, Matlock A Jeffries, Dawid Makosa, Anita Jopkiewicz, Padmaja Mehta-D'souza, Ravi K Komaravolu, Michael T Kinter","doi":"10.1186/s13293-024-00680-6","DOIUrl":"10.1186/s13293-024-00680-6","url":null,"abstract":"<p><strong>Background: </strong>Women have a higher risk of developing osteoarthritis (OA) than men, including with obesity. To better understand this disparity, we investigated sex differences in metabolic and inflammatory factors associated with OA using a diet-induced mouse model of obesity. We hypothesized that 20 weeks of high-fat diet (HFD) would induce sexually dimorphic changes in both systemic and local risk factors of knee OA.</p><p><strong>Methods: </strong>Male and female C57BL/6J mice were fed Chow or HFD from 6 to 26 weeks of age (n = 12 per diet and sex). We performed broad metabolic phenotyping, 16 S gut microbiome analysis, targeted gene expression analysis of synovium-infrapatellar fat tissue, targeted gene expression and proteomic analysis of articular cartilage, chondrocyte metabolic profiling, and OA histopathology. Two-way ANOVA statistics were utilized to determine the contribution of sex and diet and their interaction on outcomes.</p><p><strong>Results: </strong>Mice fed HFD weighed 1.76-fold (p < 0.0001) and 1.60-fold (p < 0.0001) more than male and female Chow cohorts, respectively, with both sexes reaching similar body fat levels (male: 43.9 ± 2.2%; female: 44.1 ± 3.8%). HFD caused greater cartilage pathology (p < 0.024) and synovial hyperplasia (p < 0.038) versus Chow in both sexes. Cartilage pathology was greater in male versus female mice (p = 0.048), and only male mice developed osteophytes with HFD (p = 0.044). Both sexes exhibited metabolic inflexibility on HFD, but only male mice developed glucose intolerance (p < 0.0001), fatty liver (p < 0.0001), and elevated serum amylase (p < 0.0001) with HFD versus Chow. HFD treatment caused sex-dependent differences in gut microbiota beta diversity (p = 0.01) and alteration in specific microbiome clades, such as a HFD-dependent reduction in abundance of Bifidobacterium only in male mice. In knee synovium and infrapatellar fat tissue, HFD upregulated the expression of pro-inflammatory and pro-fibrotic genes predominantly in female mice. In cartilage, lipid metabolism proteins were more abundant with HFD in male mice, whereas proteins involved in glycolysis/gluconeogenesis and biosynthesis of amino acids were greater in cartilage of female mice. Sex-dependent metabolic differences were observed in cartilage from young, healthy mice prior to pubertal maturation, but not in primary juvenile chondrocytes studied in vitro.</p><p><strong>Conclusions: </strong>HFD induced numerous sex differences in metabolic and inflammatory outcomes, especially in joint tissues, suggesting that sex-specific cellular processes are involved during development of early-stage OA with obesity.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"103"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-inactive-specific transcript: a long noncoding RNA with a complex role in sex differences in human disease.","authors":"Dan N Predescu, Babak Mokhlesi, Sanda A Predescu","doi":"10.1186/s13293-024-00681-5","DOIUrl":"10.1186/s13293-024-00681-5","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In humans, the X and Y chromosomes determine the biological sex, XX specifying for females and XY for males. The long noncoding RNA X-inactive specific transcript (lncRNA XIST) plays a crucial role in the process of X chromosome inactivation (XCI) in cells of the female, a process that ensures the balanced expression of X-linked genes between sexes. Initially, it was believed that XIST can be expressed only from the inactive X chromosome (Xi) and is considered a typically female-specific transcript. However, accumulating evidence suggests that XIST can be detected in male cells as well, and it participates in the development of cancers and other human diseases by regulating gene expression at epigenetic, chromatin remodeling, transcriptional, and translational levels. XIST is abnormally expressed in many sexually dimorphic diseases, including autoimmune and neurological diseases, pulmonary arterial hypertension (PAH), and some types of cancers. However, the underlying mechanisms are not fully understood. Escape from XCI and skewed XCI also contributes to sex-biased diseases and their severity. Interestingly, in humans, similar to experimental animal models of human disease, the males with the XIST gene activated display the sex-biased disease condition at a rate close to females, and significantly greater than males who had not been genetically modified. For instance, the men with supernumerary X chromosomes, such as men with Klinefelter syndrome (47, XXY), are predisposed toward autoimmunity similar to females (46, XX), and have increased risk for strongly female biased diseases, compared to 46, XY males. Interestingly, chromosome X content has been linked to a longer life span, and the presence of two chromosome X contributes to increased longevity regardless of the hormonal status. In this review, we summarize recent knowledge about XIST structure/function correlation and involvement in human disease with focus on XIST abnormal expression in males. Many human diseases show differences between males and females in penetrance, presentation, progression, and survival. In humans, the X and Y sex chromosomes determine the biological sex, XX specifying for females and XY for males. This numeric imbalance, two X chromosomes in females and only one in males, known as sex chromosome dosage inequality, is corrected in the first days of embryonic development by inactivating one of the X chromosomes in females. While this \"dosage compensation\" should in theory solve the difference in the number of genes between sexes, the expressed doses of X genes are incompletely compensated by X chromosome inactivation in females. In this review we try to highlight how abnormal expression and function of XIST, a gene on the X chromosome responsible for this inactivation process, may explain the sex differences in human health and disease. A better understanding of the molecular mechanisms of XIST participation in the male-female differences in disease is highly r","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"101"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent effects of chronic jet lag on circadian rhythm and metabolism in mice.","authors":"Tiantian Ma, Ryohei Matsuo, Kaito Kurogi, Shunsuke Miyamoto, Tatsumi Morita, Marina Shinozuka, Fuka Taniguchi, Keisuke Ikegami, Shinobu Yasuo","doi":"10.1186/s13293-024-00679-z","DOIUrl":"10.1186/s13293-024-00679-z","url":null,"abstract":"<p><strong>Background: </strong>The circadian clock integrates external environmental changes into the internal physiology of organisms. Perturbed circadian clocks due to misaligned light cycles increase the risk of diseases, including metabolic disorders. However, the effects of sex differences in this context remain unclear.</p><p><strong>Methods: </strong>Circadian misalignment was induced by a chronic jet lag (CJL) shift schedule (light-on time advanced by 6 h every 2 days) in C57BL/6N male and female mice. Core body temperature and activity rhythms were recorded using a nano tag, and the gene expression rhythms of clock and clock-controlled genes in the liver and adrenal glands were analyzed using qPCR. Glucose metabolism and insulin response were evaluated using glucose tolerance, insulin sensitivity, and glucose response assays. Castration and testosterone replacement were performed to assess the fundamental role of testosterone in male phenotypes under CJL.</p><p><strong>Results: </strong>Under CJL treatment, male mice exhibited increased weight gain, whereas females exhibited decreased weight gain compared to that of the respective controls. CJL treatment induced a lower robustness of circadian rhythms in core body temperature and a weaker rhythm of clock gene expression in the liver and adrenal glands in females, but not in males. Only male mice exhibited glucose intolerance under CJL conditions, without the development of insulin resistance. Castrated mice without testosterone exhibited decreased weight gain and reduced robustness of body temperature rhythm, as observed in intact females. Testosterone replacement in castrated mice recovered the CJL-induced weight gain, robustness of temperature rhythm, and glucose intolerance observed in intact males.</p><p><strong>Conclusions: </strong>Significant sex-based differences were observed in circadian clock organization and metabolism under CJL. Testosterone plays a crucial role in maintaining the circadian clock and regulating CJL metabolism in males.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"102"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen administration enhances the adverse effects of cigarette smoking on the heart in cycling female mice.","authors":"Emna Abidi, Reine Diab, Rana Zahreddine, Ghadir Amin, Abdullah Kaplan, George W Booz, Fouad A Zouein","doi":"10.1186/s13293-024-00667-3","DOIUrl":"10.1186/s13293-024-00667-3","url":null,"abstract":"<p><p>Smoking, particularly chronic smoking (CS), is a threat to global health, contributing to increased mortality and morbidity associated with cardiovascular disease (CVD). CS induces oxidative stress and endothelial dysfunction, which has a profound impact on cardiac structure and function. While the protective effects of estrogen, particularly 17β-estradiol (E2), on cardiovascular health are well-documented in premenopausal women, the interaction between estrogen and CS remains poorly understood. The aim of this study is to investigate the impact of chronic cigarette smoking on cardiac health in relation to ethinylestradiol (EE) oral contraceptive (OC) usage in premenopausal females. Female mice were exposed to chronic cigarette smoke and co-administered EE. Cardiac structural and functional parameters were assessed alongside inflammatory markers, oxidative stress indicators, and histological changes. Results revealed that the combination of EE and CS led to adverse cardiac remodeling characterized by increased left ventricular end-diastolic volume and elevated left ventricular mass. In addition, an inflammatory state was evident, marked by increased expression of IL-4, IL-1β, IL-13, IL-10, and PARP-1, as well as increased interstitial collagen deposition. These findings suggest a progression towards adverse cardiac remodeling resembling dilated cardiomyopathy. Furthermore, our observations highlight the complexity of the inflammatory response triggered by smoking, potentially exacerbated by estrogen supplementation. The main finding of this study is that the combination of CS and EE enhanced adverse cardiac remodeling, which was shown structurally, histologically, and biochemically.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"100"},"PeriodicalIF":4.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embracing sex-specific differences in engineered kidney models for enhanced biological understanding of kidney function.","authors":"Charlotte Veser, Aurélie Carlier, Vanessa Dubois, Silvia M Mihăilă, Sangita Swapnasrita","doi":"10.1186/s13293-024-00662-8","DOIUrl":"10.1186/s13293-024-00662-8","url":null,"abstract":"<p><p>In vitro models serve as indispensable tools for advancing our understanding of biological processes, elucidating disease mechanisms, and establishing screening platforms for drug discovery. Kidneys play an instrumental role in the transport and elimination of drugs and toxins. Nevertheless, despite the well-documented inter-individual variability in kidney function and the multifaceted nature of renal diseases-spanning from their origin, trigger and which segment of the kidney is affected-to presentation, progression and prognosis, few studies take into consideration the variable of sex. Notably, the inherent disparities between female and male biology warrants a more comprehensive representation within in vitro models of the kidney. The omission of sex as a fundamental biological variable carries the substantial risk of overlooking sex-specific mechanisms implicated in health and disease, along with potential differences in drug responsiveness and toxicity profiles between sexes. This review emphasizes the importance of incorporating cellular, biological and functional sex-specific features of renal activity in health and disease in in vitro models. For that, we thoroughly document renal sex-specific features and propose a strategic experimental framework to integrate sex-based differences into human kidney in vitro models by outlining critical design criteria to elucidate sex-based features at cellular and tissue levels. The goal is to enhance the accuracy of models to unravel renal mechanisms, and improve our understanding of their impact on drug efficacy and safety profiles, paving the way for a more comprehensive understanding of patient-specific treatment modalities.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"99"},"PeriodicalIF":4.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health.","authors":"Liyuan Ran, Xiaoshuang Wang, Rui Ma, Haoan Wang, Yingjie Wu, Zichao Yu","doi":"10.1186/s13293-024-00676-2","DOIUrl":"https://doi.org/10.1186/s13293-024-00676-2","url":null,"abstract":"<p><strong>Background: </strong>The global incidence of obesity continues to rise, which increases the prevalence of metabolic diseases. We previously demonstrated the beneficial effect of adipose-specific growth hormone receptor (Ghr) knockout (KO) on metabolic parameters in male mice exposed to high fat diet. Although the effect of the growth hormone (GH) axis on lipid metabolism has been well studied, sexual dimorphism has not been considered. Furthermore, the effects of the GH axis on intergenerational adipose development are understudied. The present study aimed to evaluate whether adipose-specific Ghr knockout is associated with sex-specific differences in metabolic health of female offspring.</p><p><strong>Methods: </strong>Ghr^flox/flox (LL) mice were crossed with Adipoq-Cre mice to generate adipose-specific Ghr knockout (KO) mice. Physiological phenotype and fertility of female LL and KO mice were measured. Body weight, organ weight, glucose homeostasis, liver and adipose histology, hepatic triglycerides (TG) content, serum TG and low-density lipoprotein cholesterol (LDL-C) levels of female offspring were detected.</p><p><strong>Results: </strong>We found an increase in adipocyte size in female KO mice, but no change in glucose tolerance or insulin sensitivity. Adipose-specific Ghr deficiency impairs fertility in female KO mice. Maternal adipose-specific Ghr deficiency had a considerable beneficial effect on glucose metabolism in female offspring. The female offspring of the KO mice were protected against diet-induced obesity and the degree of hepatic steatosis and hyperlipidemia was reduced. The adipocyte size of the KO offspring did not change significantly despite the decrease in fat weight. Furthermore, the phenotypes of the offspring of LL mice fostered by the KO mothers differed from those of offspring remaining in the maternal nest.</p><p><strong>Conclusions: </strong>The findings of our study suggest that adipose GH axis plays a complex and important role in the intergenerational effects of metabolic health and adipocytes on offspring in a sex-specific manner. Future studies are needed to reveal the mechanisms of these sexually dimorphic phenotypes and the feasibility of providing new interventions for improving offspring metabolic health.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"98"},"PeriodicalIF":4.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influences of sex and gender on the associations between risk and protective factors, brain, and behavior.","authors":"Katharina Brosch, Elvisha Dhamala","doi":"10.1186/s13293-024-00674-4","DOIUrl":"10.1186/s13293-024-00674-4","url":null,"abstract":"<p><p>Risk and protective factors for psychiatric illnesses are linked to distinct structural and functional changes in the brain. Further, the prevalence of these factors varies across sexes and genders, yet the distinct and joint effects of sex and gender in this context have not been extensively characterized. This suggests that risk and protective factors may map onto the brain and uniquely influence individuals across sexes and genders. Here, we review how specific risk (childhood maltreatment, the COVID-19 pandemic, experiences of racism), and protective factors (social support and psychological resilience) distinctly influence the brain across sexes and genders. We also discuss the role of sex and gender in the compounding effects of risk factors and in the interdependent influences of risk and protective factors. As such, we call on researchers to consider sex and gender when researching risk and protective factors for psychiatric illnesses, and we provide concrete recommendations on how to account for them in future research. Considering protective factors alongside risk factors in research and acknowledging sex and gender differences will enable us to establish sex- and gender-specific brain-behavior relationships. This will subsequently inform the development of targeted prevention and intervention strategies for psychiatric illnesses, which have been lacking. To achieve sex and gender equality in mental health, acknowledging and researching potential differences will lead to a better understanding of men and women, males and females, and the factors that make them more vulnerable or resilient to psychopathology.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"97"},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age- and sex-associated alterations in hypothalamic mitochondrial bioenergetics and inflammatory-associated signaling in the 3xTg mouse model of Alzheimer's disease.","authors":"Aida Adlimoghaddam, Kyle M Fontaine, Benedict C Albensi","doi":"10.1186/s13293-024-00671-7","DOIUrl":"10.1186/s13293-024-00671-7","url":null,"abstract":"<p><p>Mitochondrial dysfunction and associated inflammatory signaling are pivotal in both aging and in Alzheimer's disease (AD). Studies have also shown that hypothalamic function is affected in AD. The hypothalamus may be a target for AD drugs given that mitochondrial alterations are observed in the hypothalamus. This study investigated how age and sex affect mitochondrial bioenergetics and inflammatory signaling in the hypothalamic mitochondria of 3xTg and control mice at 2, 6, and 13 months, aiming to enhance our understanding of these processes in aging and AD. Parameters included oxygen consumption rates, expression levels of subunits comprising mitochondrial complexes I-V, the enzymatic activity of cytochrome c oxidase (COX), transcription factors associated with inflammation such as NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers. Hypothalamic mitochondrial dysfunction was observed in 3xTg females as early as 2 months, but no changes were detected in 3xTg males until 6 months of age. In 3xTg mice, subunit expression levels for mitochondrial complexes I-II were significantly reduced in both sexes. Significant sex-based differences in COX activity were also observed at 13 months of age, with levels being lower in females compared to males. In addition, significant sex differences were indicated in NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers at different age groups during normal aging and AD progression. These findings highlight important sex differences in hypothalamic bioenergetics and inflammation, offering insights into potential new targets for preventing and/or treating AD.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"95"},"PeriodicalIF":4.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}