Biology of Sex Differences最新文献

{"title":"XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner","authors":"Carly J. Amato-Menker, Quinn Hopen, Andrea Pettit, Jasleen Gandhi, Gangqing Hu, Rosana Schafer, Jennifer Franko","doi":"10.1186/s13293-024-00597-0","DOIUrl":"https://doi.org/10.1186/s13293-024-00597-0","url":null,"abstract":"Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation. Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation. XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies. FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism. Male and female immune systems differ in their ability to respond to infectious challenge. While males tend to be more susceptible to infection and produce lower amounts of antibodies in response to vaccination, females are more prone to develop autoimmune and inflammatory diseases. Key contributors to these differences include sex hormones, sex chromosome complement (XX in females vs. XY in males), and distinct gut microbial communities capable of regulating immune activation. While ","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"24 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125841","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":"Microbial composition, functionality, and stress resilience or susceptibility: unraveling sex-specific patterns.","authors":"Arax Tanelian, Bistra Nankova, Mariam Miari, Esther L Sabban","doi":"10.1186/s13293-024-00590-7","DOIUrl":"10.1186/s13293-024-00590-7","url":null,"abstract":"<p><strong>Background: </strong>Following exposure to traumatic stress, women are twice as likely as men to develop mood disorders. Yet, individual responses to such stress vary, with some people developing stress-induced psychopathologies while others exhibit resilience. The factors influencing sex-related disparities in affective disorders as well as variations in resilience remain unclear; however, emerging evidence suggests differences in the gut microbiota play a role. In this study, using the single prolonged stress (SPS) model of post-traumatic stress disorder, we investigated pre- and post-existing differences in microbial composition, functionality, and metabolites that affect stress susceptibility or resilience in each sex.</p><p><strong>Methods: </strong>Male and female Sprague-Dawley rats were randomly assigned to control or SPS groups. Two weeks following SPS, the animals were exposed to a battery of behavioral tests and decapitated a day later. Based on their anxiety index, they were further categorized as SPS-resilient (SPS-R) or SPS-susceptible (SPS-S). On the day of dissection, cecum, and selected brain tissues were isolated. Stool samples were collected before and after SPS, whereas urine samples were taken before and 30 min into the SPS.</p><p><strong>Results: </strong>Before SPS exposure, the sympathoadrenal axis exhibited alterations within male subgroups only. Expression of tight junction protein claudin-5 was lower in brain of SPS-S males, but higher in SPS-R females following SPS. Across the study, alpha diversity remained consistently lower in males compared to females. Beta diversity revealed distinct separations between male and female susceptible groups before SPS, with this separation becoming evident in the resilient groups following SPS. At the genus level, Lactobacillus, Lachnospiraceae_Incertae_Sedis, and Barnesiella exhibited sex-specific alterations, displaying opposing abundances in each sex. Additionally, sex-specific changes were observed in microbial predictive functionality and targeted functional modules both before and after SPS. Alterations in the microbial short-chain fatty acids (SCFAs), were also observed, with major and minor SCFAs being lower in SPS-susceptible males whereas branched-chain SCFAs being higher in SPS-susceptible females.</p><p><strong>Conclusion: </strong>This study highlights distinct pre- and post-trauma differences in microbial composition, functionality, and metabolites, associated with stress resilience in male and female rats. The findings underscore the importance of developing sex-specific therapeutic strategies to effectively address stress-related disorders. Highlights SPS model induces divergent anxiety and social behavioral responses to traumatic stress in both male and female rodents. SPS-resilient females displayed less anxiety-like behavior and initiated more interactions towards a juvenile rat than SPS-resilient males. Sex-specific pre-existing and SPS-induced differen","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"20"},"PeriodicalIF":7.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970870","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":"Consideration of sex as a biological variable in diabetes research across twenty years","authors":"Celena M. Cherian, Hayley R. Reeves, Duneesha De Silva, Serena Tsao, Katie E. Marshall, Elizabeth J. Rideout","doi":"10.1186/s13293-024-00595-2","DOIUrl":"https://doi.org/10.1186/s13293-024-00595-2","url":null,"abstract":"Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field. We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable. Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research. Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies. Men and women have a different risk of developing type 1 and type 2 diabetes. Men and women also live with different complications of diabetes and show different treatment benefits. One reason for these differences is that biological sex affects diabetes risk, complications, and treatment efficacy. Unfortunately, a lot of diabetes research does not consider whether biological sex might affect the study results. As a result, we do not have enough information to match an individual’s sex with the best diabetes prevention and treatment strategies. We are tackling this problem by learning how diabetes researchers conside","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"31 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968621","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-specific modulation of early life vocalization and cognition by Fmr1 gene dosage in a mouse model of Fragile X Syndrome","authors":"Gabriele Giua, Daniela Iezzi, Alba Caceres-Rodriguez, Benjamin Strauss, Pascale Chavis, Olivier J. Manzoni","doi":"10.1186/s13293-024-00594-3","DOIUrl":"https://doi.org/10.1186/s13293-024-00594-3","url":null,"abstract":"Pup-dam ultrasonic vocalizations (USVs) are essential to cognitive and socio-emotional development. In autism and Fragile X Syndrome (FXS), disruptions in pup-dam USV communication hint at a possible connection between abnormal early developmental USV communication and the later emergence of communication and social deficits. Here, we gathered USVs from PND 10 FXS pups during a short period of separation from their mothers, encompassing animals of all possible genotypes and both sexes (i.e., Fmr1-/y vs. Fmr1+/y males and Fmr1+/+, +/-, and -/- females). This allowed comparing the influence of sex and gene dosage on pups’ communication capabilities. Leveraging DeepSqueak and analyzing vocal patterns, intricate vocal behaviors such as call structure, duration, frequency modulation, and temporal patterns were examined. Furthermore, homing behavior was assessed as a sensitive indicator of early cognitive development and social discrimination. This behavior relies on the use of olfactory and thermal cues to navigate and search for the maternal or nest odor in the surrounding space. The results show that FMRP-deficient pups of both sexes display an increased inclination to vocalize when separated from their mothers, and this behavior is accompanied by significant sex-specific changes in the main features of their USVs as well as in body weight. Analysis of the vocal repertoire and syntactic usage revealed that Fmr1 gene silencing primarily alters the USVs’ qualitative composition in males. Moreover, sex-specific effects of Fmr1 silencing on locomotor activity and homing behavior were observed. FMRP deficiency in females increased activity, reduced nest-reaching time, and extended nest time. In males, it prolonged nest-reaching time and reduced nest time without affecting locomotion. These findings highlight the interplay between Fmr1 gene dosage and sex in influencing communicative and cognitive skills during infancy. In this study, we investigated ultrasonic vocalizations (USVs) and homing behavior in a mouse model of Fragile X Syndrome (FXS), a leading genetic cause of autism spectrum disorder (ASD) caused by a mutation of the X-chromosome linked Fmr1 gene. Disruptions in pup-dam USV communication and cognitive skills may be linked to the later emergence of communication and social deficits in ASD. USVs were collected from 10-day-old FXS pups of all possible genotypes and both sexes during a short period of separation from their mothers. We utilized DeepSqueak, an advanced deep learning system, to examine vocal patterns and intricate vocal behaviors, including call structure, duration, frequency modulation, and their temporal patterns. Homing, a sensitive indicator of early cognitive development and social discrimination was assessed at P13. The results showed that FXS pups of both sexes displayed an increased inclination to vocalize when separated from their mothers. Examination of the vocal repertoire and its syntactic usage revealed that the silenc","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"194 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139923472","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":"Different mechanisms underlie compulsive alcohol self-administration in male and female rats","authors":"Sanne Toivainen, Li Xu, Francesco Gobbo, Andrea Della Valle, Andrea Coppola, Markus Heilig, Esi Domi","doi":"10.1186/s13293-024-00592-5","DOIUrl":"https://doi.org/10.1186/s13293-024-00592-5","url":null,"abstract":"Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences (“compulsive use”). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors. Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study. Unpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle. Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction. Sex plays an important role in the progression and treatment of alcohol addiction. While men show a higher prevalence of alcohol addiction, women are more susceptible to the adverse effects of excessive alcohol consumption. Additionally, women often rely on heavy drinking as a maladaptive coping mechanism to alleviate stress and anxiety, driven by negative affect. On the other hand, men are more likely to report heavy drinking and relapse in response to positive emotions and social influences. These sex-based differences underline the importance of unders","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"3 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751655","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":"Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats.","authors":"Ryan T McCallum, Rachel-Karson Thériault, Joshua D Manduca, Isaac S B Russell, Angel M Culmer, Janan Shoja Doost, Tami A Martino, Melissa L Perreault","doi":"10.1186/s13293-024-00589-0","DOIUrl":"10.1186/s13293-024-00589-0","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a recurring affective disorder that is two times more prevalent in females than males. Evidence supports immune system dysfunction as a major contributing factor to MDD, notably in a sexually dimorphic manner. Nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of antioxidant signalling during inflammation, is dysregulated in many chronic inflammatory disorders; however, its role in depression and the associated sex differences have yet to be explored. Here, we investigated the sex-specific antidepressant and immunomodulatory effects of the potent Nrf2 activator dimethyl fumarate (DMF), as well as the associated gene expression profiles.</p><p><strong>Methods: </strong>Male and female rats were treated with vehicle or DMF (25 mg/kg) whilst subjected to 8 weeks of chronic unpredictable stress. The effect of DMF treatment on stress-induced depression- and anxiety-like behaviours, as well as deficits in recognition and spatial learning and memory were then assessed. Sex differences in hippocampal (HIP) microglial activation and gene expression response were also evaluated.</p><p><strong>Results: </strong>DMF treatment during stress exposure had antidepressant effects in male but not female rats, with no anxiolytic effects in either sex. Recognition learning and memory and spatial learning and memory were impaired in chronically stressed males and females, respectively, and DMF treatment rescued these deficits. DMF treatment also prevented stress-induced HIP microglial activation in males. Conversely, females displayed no HIP microglial activation associated with stress exposure. Last, chronic stress elicited sex-specific alterations in HIP gene expression, many of which were normalized in animals treated with DMF. Of note, most of the differentially expressed genes in males normalized by DMF were related to antioxidant, inflammatory or immune responses.</p><p><strong>Conclusions: </strong>Collectively, these findings support a greater role of immune processes in males than females in a rodent model of depression. This suggests that pharmacotherapies that target Nrf2 have the potential to be an effective sex-specific treatment for depression.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"16"},"PeriodicalIF":7.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728882","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 differences in the effects of individual anxiety state on regional responses to negative emotional scenes.","authors":"Shefali Chaudhary, Hak Kei Wong, Yu Chen, Sheng Zhang, Chiang-Shan R Li","doi":"10.1186/s13293-024-00591-6","DOIUrl":"10.1186/s13293-024-00591-6","url":null,"abstract":"<p><strong>Background: </strong>Men and women are known to show differences in the incidence and clinical manifestations of mood and anxiety disorders. Many imaging studies have investigated the neural correlates of sex differences in emotion processing. However, it remains unclear how anxiety might impact emotion processing differently in men and women.</p><p><strong>Method: </strong>We recruited 119 healthy adults and assessed their levels of anxiety using State-Trait Anxiety Inventory (STAI) State score. With functional magnetic resonance imaging (fMRI), we examined regional responses to negative vs. neutral (Neg-Neu) picture matching in the Hariri task. Behavioral data were analyzed using regression and repeated-measures analysis of covariance with age as a covariate, and fMRI data were analyzed using a full-factorial model with sex as a factor and age as a covariate.</p><p><strong>Results: </strong>Men and women did not differ in STAI score, or accuracy rate or reaction time (RT) (Neg-Neu). However, STAI scores correlated positively with RT (Neg-Neu) in women but not in men. Additionally, in women, STAI score correlated positively with lingual gyrus (LG) and negatively with medial prefrontal cortex (mPFC) and superior frontal gyrus (SFG) activity during Neg vs. Neu trials. The parameter estimates (βs) of mPFC also correlated with RT (Neg-Neu) in women but not in men. Generalized psychophysiological interaction (gPPI) analysis in women revealed mPFC connectivity with the right inferior frontal gyrus, right SFG, and left parahippocampal gyrus during Neg vs. Neu trials in positive correlation with both STAI score and RT (Neg-Neu). In a mediation analysis, mPFC gPPI but not mPFC activity fully mediated the association between STAI scores and RT (Neg-Neu).</p><p><strong>Conclusion: </strong>With anxiety affecting the behavioral and neural responses to negative emotions in women but not in men and considering the known roles of the mPFC in emotion regulation, we discussed heightened sensitivity and regulatory demands during negative emotion processing as neurobehavioral markers of anxiety in women.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"15"},"PeriodicalIF":7.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728883","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":"Remembering the null hypothesis when searching for brain sex differences.","authors":"Lise Eliot","doi":"10.1186/s13293-024-00585-4","DOIUrl":"10.1186/s13293-024-00585-4","url":null,"abstract":"<p><p>Human brain sex differences have fascinated scholars for centuries and become a key focus of neuroscientists since the dawn of MRI. We recently published a major review in Neuroscience and Biobehavioral Reviews showing that most male-female brain differences in humans are small and few have been reliably replicated. Although widely cited, this work was the target of a critical Commentary by DeCasien et al. (Biol Sex Differ 13:43, 2022). In this response, I update our findings and confirm the small effect sizes and pronounced scatter across recent large neuroimaging studies of human sex/gender difference. Based on the sum of data, neuroscientists would be well-advised to take the null hypothesis seriously: that men and women's brains are fundamentally similar, or \"monomorphic\". This perspective has important implications for how we study the genesis of behavioral and neuropsychiatric gender disparities.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"14"},"PeriodicalIF":7.9,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711293","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":"The role of microRNAs in understanding sex-based differences in Alzheimer's disease.","authors":"Jaime Llera-Oyola, Héctor Carceller, Zoraida Andreu, Marta R Hidalgo, Irene Soler-Sáez, Fernando Gordillo, Borja Gómez-Cabañes, Beatriz Roson, Maria de la Iglesia-Vayá, Roberta Mancuso, Franca R Guerini, Akiko Mizokami, Francisco García-García","doi":"10.1186/s13293-024-00588-1","DOIUrl":"10.1186/s13293-024-00588-1","url":null,"abstract":"<p><strong>Background: </strong>The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.</p><p><strong>Methods: </strong>A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.</p><p><strong>Results: </strong>Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.</p><p><strong>Conclusions: </strong>Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"13"},"PeriodicalIF":7.9,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650236","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 differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression.","authors":"Xiaofeng Lan, Haiyan Liu, Chengyu Wang, Weicheng Li, Fan Zhang, Zhibo Hu, Xiaoyu Chen, Zerui You, Yuping Ning, Yanling Zhou","doi":"10.1186/s13293-024-00587-2","DOIUrl":"10.1186/s13293-024-00587-2","url":null,"abstract":"<p><strong>Background: </strong>Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.</p><p><strong>Methods: </strong>A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).</p><p><strong>Results: </strong>Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).</p><p><strong>Conclusions: </strong>Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"12"},"PeriodicalIF":4.9,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575224","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}