Biology of Sex Differences最新文献

{"title":"TrkB-mediated sustained neuroprotection is sex-specific and (text{ER}alpha)-dependent in adult mice following neonatal hypoxia ischemia","authors":"Vishal Chanana, Margaret Hackett, Nazli Deveci, Nur Aycan, Burak Ozaydin, Nur Sena Cagatay, Damla Hanalioglu, Douglas B. Kintner, Karson Corcoran, Sefer Yapici, Furkan Camci, Jens Eickhoff, Karyn M. Frick, Peter Ferrazzano, Jon E. Levine, Pelin Cengiz","doi":"10.1186/s13293-023-00573-0","DOIUrl":"https://doi.org/10.1186/s13293-023-00573-0","url":null,"abstract":"Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of $$text{ER}alpha$$ . These findings demonstrated that TrkB activation in the presence of $$text{ER}alpha$$ comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of $$text{ER}alpha$$ -dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. In this study, we used a unilateral hypoxic ischemic (HI) mouse model. $$text{ER}alpha$$ +/+ or $$text{ER}alpha$$ −/− mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry. Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking $$text{ER}alpha$$ . The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were $$text{ER}alpha$$ -dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked $$text{ER}alpha$$ . When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of $$text{ER}alpha$$ significantly reduced overall HI-associated mortality in both sexes. These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are $$text{ER}alpha$$ -associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner. Periods of low oxygen delivery and blood flow to the brains of newborns are known to cause life-long impairments ","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"24 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092483","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":"Univariate and multivariate sex differences and similarities in gray matter volume within essential language-processing areas","authors":"Carla Sanchis-Segura, Rand R. Wilcox, Alvaro Javier Cruz-Gómez, Sonia Félix-Esbrí, Alba Sebastián-Tirado, Cristina Forn","doi":"10.1186/s13293-023-00575-y","DOIUrl":"https://doi.org/10.1186/s13293-023-00575-y","url":null,"abstract":"Sex differences in language-related abilities have been reported. It is generally assumed that these differences stem from a different organization of language in the brains of females and males. However, research in this area has been relatively scarce, methodologically heterogeneous and has yielded conflicting results. Univariate and multivariate sex differences and similarities in gray matter volume (GMVOL) within 18 essential language-processing brain areas were assessed in a sex-balanced sample (N = 588) of right-handed young adults. Univariate analyses involved location, spread, and shape comparisons of the females’ and males’ distributions and were conducted with several robust statistical methods able to quantify the size of sex differences and similarities in a complementary way. Multivariate sex differences and similarities were estimated by the same methods in the continuous scores provided by two distinct multivariate procedures (logistic regression and a multivariate analog of the Wilcoxon–Mann–Whitney test). Additional analyses were addressed to compare the outcomes of these two multivariate analytical strategies and described their structure (that is, the relative contribution of each brain area to the multivariate effects). When not adjusted for total intracranial volume (TIV) variation, “large” univariate sex differences (males > females) were found in all 18 brain areas considered. In contrast, “small” differences (females > males) in just two of these brain areas were found when controlling for TIV. The two multivariate methods tested provided very similar results. Multivariate sex differences surpassed univariate differences, yielding \"large\" differences indicative of larger volumes in males when calculated from raw GMVOL estimates. Conversely, when calculated from TIV-adjusted GMVOL, multivariate differences were \"medium\" and indicative of larger volumes in females. Despite their distinct size and direction, multivariate sex differences in raw and TIV-adjusted GMVOL shared a similar structure and allowed us to identify the components of the SENT_CORE network which more likely contribute to the observed effects. Our results confirm and extend previous findings about univariate sex differences in language-processing areas, offering unprecedented evidence at the multivariate level. We also observed that the size and direction of these differences vary quite substantially depending on whether they are estimated from raw or TIV-adjusted GMVOL measurements. While it is generally assumed that there is a distinct organization of language in the brains of females and males, studies investigating potential sex-based differences in language-related neural circuits have been characterized by their methodological heterogeneity and yielded inconclusive results. In this study, we explored how the brains of men and women differ in a well-defined network of brain areas essential for basic language functions. We found that there are indeed dif","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"10 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825507","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 and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains","authors":"Masahiro Morishita, Shimpei Higo, Kinuyo Iwata, Hirotaka Ishii","doi":"10.1186/s13293-023-00574-z","DOIUrl":"https://doi.org/10.1186/s13293-023-00574-z","url":null,"abstract":"ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506). To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch’s t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey–Kramer test were used for comparisons among multiple groups with different estrogen treatments. ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers. Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain. Although the brain is a major target organ of estrogens, the distribution of estrogen receptors in the brain is not fully understood. ESR2, also known as estrogen receptor β, is an estrogen receptor subtype; its localization in the brain has long been controversial because it has traditionally been difficult to detect. In the present study, we analyzed the expression sites of ESR2 in mouse and rat brains using immunohistochemistry with a well-validated antibody, PPZ0506. The immunohistochemical analysis revealed a more localized expression of ESR2 protein in brain subregions than has previously been reported. Additionally, there were clear sex and interspecies differences in the distribution of this protein. We also observed changes in ESR2 expression in the female brain in response to circulating estrogen levels. Our results, which show the precise expression profiles of ESR2 prote","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"6 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715148","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 differences in type 2 diabetes: an opportunity for personalized medicine","authors":"Meredith L. Johnson, Joshua D. Preston, Cetewayo S. Rashid, Kevin J. Pearson, J. Nina Ham","doi":"10.1186/s13293-023-00571-2","DOIUrl":"https://doi.org/10.1186/s13293-023-00571-2","url":null,"abstract":"Over the past several decades, substantial ground has been gained in understanding the biology of sex differences. With new mandates to include sex as a biological variable in NIH-funded research, greater knowledge is forthcoming on how sex chromosomes, sex hormones, and social and societal differences between sexes can affect the pathophysiology of health and disease. A detailed picture of how biological sex impacts disease pathophysiology will directly inform clinicians in their treatment approaches and challenge canonical therapeutic strategies. Thus, a profound opportunity to explore sex as a variable in personalized medicine now presents itself. While many sex differences are apparent in humans and have been described at length, we are only beginning to see how such differences impact disease progression, treatment efficacy, and outcomes in obesity, type 2 diabetes, and cardiovascular disease. Here, we briefly present the most salient and convincing evidence of sex differences in type 2 diabetes detection, diagnostics, disease course, and therapeutics. We then offer commentary on how this evidence can inform clinicians on how to approach the clinical workup and management of different patients with diabetes. Finally, we discuss some gaps that remain in the literature and propose several research questions to guide basic and translational researchers as they continue in this growing area of scientific exploration. For decades, most research in the laboratory and clinical settings focused primarily on males. However, more recently, grant-funding agencies, including the National Institutes of Health, have prioritized research that studies both males and females. This has dramatically improved our understanding of how biological sex impacts whether a person is at higher risk for developing a particular disease and what treatment options may be best to achieve the healthiest outcomes. This article offers the perspectives of practicing physicians and scientists on how our knowledge about biological sex may impact disease incidence, progression, treatment options, and outcomes in obesity, diabetes, and heart disease. The piece will offer a broad overview of the current science and personalized medicine approaches in these areas. It then discusses gaps in our knowledge and proposes several questions to guide future research.","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"141 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138581345","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 bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene","authors":"Alba Hernangomez-Laderas, Ariadna Cilleros-Portet, Silvia Martínez Velasco, Sergi Marí, María Legarda, Bárbara Paola González-García, Carlos Tutau, Iraia García-Santisteban, Iñaki Irastorza, Nora Fernandez-Jimenez, Jose Ramon Bilbao","doi":"10.1186/s13293-023-00572-1","DOIUrl":"https://doi.org/10.1186/s13293-023-00572-1","url":null,"abstract":"Celiac disease (CeD) is an immune-mediated disorder that develops in genetically predisposed individuals upon gluten consumption. HLA risk alleles explain 40% of the genetic component of CeD, so there have been continuing efforts to uncover non-HLA loci that can explain the remaining heritability. As in most autoimmune disorders, the prevalence of CeD is significantly higher in women. Here, we investigated the possible involvement of the X chromosome on the sex bias of CeD. We performed a X chromosome-wide association study (XWAS) and a gene-based association study in women from the CeD Immunochip (7062 cases, 5446 controls). We also constructed a database of X chromosome cis-expression quantitative trait loci (eQTLs) in monocytes from unstimulated (n = 226) and lipopolysaccharide (LPS)-stimulated (n = 130) female donors and performed a Summary-data-based MR (SMR) analysis to integrate XWAS and eQTL information. We interrogated the expression of the potentially causal gene (TMEM187) in peripheral blood mononuclear cells (PBMCs) from celiac patients at onset, on a gluten-free diet, potential celiac patients and non-celiac controls. The XWAS and gene-based analyses identified 13 SNPs and 25 genes, respectively, 22 of which had not been previously associated with CeD. The X chromosome cis-eQTL analysis found 18 genes with at least one cis-eQTL in naïve female monocytes and 8 genes in LPS-stimulated female monocytes, 2 of which were common to both situations and 6 were unique to LPS stimulation. SMR identified a potentially causal association of TMEM187 expression in naïve monocytes with CeD in women, regulated by CeD-associated, eQTL-SNPs rs7350355 and rs5945386. The CeD-risk alleles were correlated with lower TMEM187 expression. These results were replicated using eQTLs from LPS-stimulated monocytes. We observed higher levels of TMEM187 expression in PBMCs from female CeD patients at onset compared to female non-celiac controls, but not in male CeD individuals. Using X chromosome genotypes and gene expression data from female monocytes, SMR has identified TMEM187 as a potentially causal candidate in CeD. Further studies are needed to understand the implication of the X chromosome in the higher prevalence of CeD in women. Celiac disease (CeD) is an immune-related condition triggered by gluten consumption in genetically susceptible individuals. Women present higher prevalence of CeD than men, but the biological explanation of such difference has not been elucidated. In this study, we investigated whether specific genetic variations on the X chromosome were associated with CeD in each sex. Surprisingly, we found 13 genetic variants and 25 genes significantly linked to CeD in women, but not in men. Additionally, we identified genetic variants on the X chromosome associated with gene expression of monocytes, a type of immune cells that is activated in CeD after gluten intake. Integrating these data with our previous findings, we found that lower express","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"37 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567403","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 differences in mouse infralimbic cortex projections to the nucleus accumbens shell","authors":"Caroline S. Johnson, Andrew D. Chapp, Erin B. Lind, Mark J. Thomas, Paul G. Mermelstein","doi":"10.1186/s13293-023-00570-3","DOIUrl":"https://doi.org/10.1186/s13293-023-00570-3","url":null,"abstract":"The nucleus accumbens (NAc) is an important region in motivation and reward. Glutamatergic inputs from the infralimbic cortex (ILC) to the shell region of the NAc (NAcSh) have been implicated in driving the motivation to seek reward through repeated action-based behavior. While this has primarily been studied in males, observed sex differences in motivational circuitry and behavior suggest that females may be more sensitive to rewarding stimuli. These differences have been implicated for the observed vulnerability in women to substance use disorders. We used an optogenetic self-stimulation task in addition to ex vivo electrophysiological recordings of NAcSh neurons in mouse brain slices to investigate potential sex differences in ILC-NAcSh circuitry in reward-seeking behavior. Glutamatergic neurons in the ILC were infected with an AAV delivering DNA encoding for channelrhodopsin. Entering the designated active corner of an open field arena resulted in photostimulation of the ILC terminals in the NAcSh. Self-stimulation occurred during two consecutive days of testing over three consecutive weeks: first for 10 Hz, then 20 Hz, then 30 Hz. Whole-cell recordings of medium spiny neurons in the NAcSh assessed both optogenetically evoked local field potentials and intrinsic excitability. Although both sexes learned to seek the active zone, within the first day, females entered the zone more than males, resulting in a greater amount of photostimulation. Increasing the frequency of optogenetic stimulation amplified female reward-seeking behavior. Males were less sensitive to ILC stimulation, with higher frequencies and repeated days required to increase male reward-seeking behavior. Unexpectedly, ex vivo optogenetic local field potentials in the NAcSh were greater in slices from male animals. In contrast, female medium-spiny neurons (MSNs) displayed significantly greater intrinsic neuronal excitability. Taken together, these data indicate that there are sex differences in the motivated behavior driven by glutamate within the ILC-NAcSh circuit. Though glutamatergic signaling was greater in males, heightened intrinsic excitability in females appears to drive this sex difference. The shell region of the nucleus accumbens (NAcSh) is involved in motivation and reward. It receives excitatory glutamatergic inputs from multiple brain regions. One specific region is the infralimbic cortex (ILC), which when activated, influences reward-seeking behavior. While previous research has focused on males, there are inherent sex differences in reward circuitry and reward-seeking behavior. Using an optogenetic self-stimulation task, in addition to ex vivo electrophysiological recordings, we found inherent sex differences in the ILC-NAcSh circuit in behavioral output, synaptic strength, and intrinsic neurophysiology. Female mice showed more robust reward-seeking behavior. Increasing the frequency of stimulation intensified this behavior in females, while males required higher","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"12 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567157","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 differences in the rapid detection of neutral faces associated with emotional value.","authors":"Akie Saito, Wataru Sato, Sakiko Yoshikawa","doi":"10.1186/s13293-023-00567-y","DOIUrl":"10.1186/s13293-023-00567-y","url":null,"abstract":"<p><strong>Background: </strong>Rapid detection of faces with emotional meaning is essential for understanding the emotions of others, possibly promoting successful interpersonal relationships. Although few studies have examined sex differences in the ability to detect emotional faces, it remains unclear whether faces with emotional meaning capture the attention of females and males differently, because emotional faces have visual saliency that modulates visual attention. To overcome this issue, we tested the rapid detection of the neutral faces associated with and without learned emotional value, which are all regarded as free from visual saliency. We examined sex differences in the rapid detection of the neutral female and male faces associated with emotional value.</p><p><strong>Methods: </strong>First, young adult female and male participants completed an associative learning task in which neutral faces were associated with either monetary rewards, monetary punishments, or no monetary outcomes, such that the neutral faces acquired positive, negative, and no emotional value, respectively. Then, they engaged in a visual search task in which previously learned neutral faces were presented as discrepant faces among newly presented neutral distractor faces. During the visual search task, the participants were required to rapidly identify discrepant faces.</p><p><strong>Results: </strong>Female and male participants exhibited comparable learning abilities. The visual search results demonstrated that female participants achieved rapid detection of neutral faces associated with emotional value irrespective of the sex of the faces presented, whereas male participants showed this ability only for male faces.</p><p><strong>Conclusions: </strong>Our results demonstrated that sex differences in the ability to rapidly detect neutral faces with emotional value were modulated by the sex of those faces. The results suggest greater sensitivity to faces with emotional significance in females, which might enrich interpersonal communication, regardless of sex.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"14 1","pages":"84"},"PeriodicalIF":7.9,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590126","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-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice.","authors":"Carlos Cuño-Gómiz, Estefanía de Gregorio, Anna Tutusaus, Patricia Rider, Nuria Andrés-Sánchez, Anna Colell, Albert Morales, Montserrat Marí","doi":"10.1186/s13293-023-00569-w","DOIUrl":"10.1186/s13293-023-00569-w","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in Western countries, evolving into metabolic dysfunction-associated steatohepatitis (MASH) with a sexual dimorphism. Fertile women exhibit lower MASLD risk than men, which diminishes post-menopause. While NKT-cell involvement in steatohepatitis is debated, discrepancies may stem from varied mouse strains used, predominantly C57BL6/J with Th1-dominant responses. Exploration of steatohepatitis, encompassing both genders, using Balb/c background, with Th2-dominant immune response, and CD1d-deficient mice in the Balb/c background (lacking Type I and Type II NKT cells) can clarify gender disparities and NKT-cell influence on MASH progression.</p><p><strong>Methods: </strong>A high fat and choline-deficient (HFCD) diet was used in male and female mice, Balb/c mice or CD1d^-/- mice in the Balb/c background that exhibit a Th2-dominant immune response. Liver fibrosis and inflammatory gene expression were measured by qPCR, and histology assessment. NKT cells, T cells, macrophages and neutrophils were assessed by flow cytometry.</p><p><strong>Results: </strong>Female mice displayed milder steatohepatitis after 6 weeks of HFCD, showing reduced liver damage, inflammation, and fibrosis compared to males. Male Balb/c mice exhibited NKT-cell protection against steatohepatitis whereas CD1d^-/- males on HFCD presented decreased hepatoprotection, increased liver fibrosis, inflammation, neutrophilic infiltration, and inflammatory macrophages. In contrast, the NKT-cell role was negligible in early steatohepatitis development in both female mice, as fibrosis and inflammation were similar despite augmented liver damage in CD1d^-/- females. Relevant, hepatic type I NKT levels in female Balb/c mice were significantly lower than in male.</p><p><strong>Conclusions: </strong>NKT cells exert a protective role against experimental steatohepatitis as HFCD-treated CD1d^-/- males had more severe fibrosis and inflammation than male Balb/c mice. In females, the HFCD-induced hepatocellular damage and the immune response are less affected by NKT cells on early steatohepatitis progression, underscoring sex-specific NKT-cell influence in MASH development.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"14 1","pages":"85"},"PeriodicalIF":7.9,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590127","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 binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice.","authors":"Jean K Rivera-Irizarry, Lia J Zallar, Olivia B Levine, Mary Jane Skelly, Jared E Boyce, Thaddeus Barney, Ruth Kopyto, Kristen E Pleil","doi":"10.1186/s13293-023-00565-0","DOIUrl":"10.1186/s13293-023-00565-0","url":null,"abstract":"<p><strong>Background: </strong>Binge alcohol drinking is a risk factor linked to numerous disease states including alcohol use disorder (AUD). While men binge drink more alcohol than women, this demographic gap is quickly shrinking, and preclinical studies demonstrate that females consistently consume more alcohol than males. Further, women are at increased risk for the co-expression of AUD with neuropsychiatric diseases such as anxiety and mood disorders. However, little is understood about chronic voluntary alcohol drinking and its long-term effects on behavior. Here, we sought to characterize sex differences in chronic binge drinking and the effects of protracted alcohol abstinence on anxiety- and affective-related behaviors in males and females.</p><p><strong>Methods: </strong>We assessed binge alcohol drinking patterns in male and female C57BL/6J mice using a modified Drinking in the Dark (DID) paradigm in which mice received home cage access to one bottle of 10% or 20% alcohol (EtOH) or water for 2 h per day on Days 1-3 and to two bottles (EtOH/H₂O + H₂O) for 24 h on Day 4 for 8 weekly cycles. Mice were then tested for the effects of protracted abstinence on avoidance, affective, and compulsive behaviors.</p><p><strong>Results: </strong>Female mice consumed more alcohol than males consistently across cycles of DID and at 2, 4, and 24-h timepoints within the day, with a more robust sex difference for 20% than 10% EtOH. Females also consumed more water than males, an effect that emerged at the later time points; this water consumption bias diminished when alcohol was available. Further, while increased alcohol consumption was correlated with decreased water consumption in males, there was no relationship between these two measures in females. Alcohol preference was higher in 10% vs. 20% EtOH for both sexes. During protracted abstinence following chronic binge drinking, mice displayed decreased avoidance behavior (elevated plus maze, open field, novelty suppressed feeding) and increased compulsive behavior (marble burying) that was especially robust in females. There was no effect of alcohol history on stress coping and negative affective behaviors (sucrose preference, forced swim test, tail suspension) in either sex.</p><p><strong>Conclusion: </strong>Female mice engaged in higher volume binge drinking than their male counterparts. Although females also consumed more water than males, their higher alcohol consumption was not driven by increased total fluid intake. Further, the effects of protracted abstinence following chronic binge drinking was driven by behavioral disinhibition that was more pronounced in females. Given the reciprocal relationship between risk-taking and alcohol use in neuropsychiatric disease states, these results have implications for sex-dependent alcohol drinking patterns and their long-term negative neuropsychiatric/physiological health outcomes in humans.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"14 1","pages":"83"},"PeriodicalIF":7.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152591","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":"Correction: Variability of temperature measurements recorded by a wearable device by biological sex.","authors":"Lauryn Keeler Bruce, Patrick Kasl, Severine Soltani, Varun K Viswanath, Wendy Hartogensis, Stephan Dilchert, Frederick M Hecht, Anoushka Chowdhary, Claudine Anglo, Leena Pandya, Subhasis Dasgupta, Ilkay Altintas, Amarnath Gupta, Ashley E Mason, Benjamin L Smarr","doi":"10.1186/s13293-023-00568-x","DOIUrl":"10.1186/s13293-023-00568-x","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"14 1","pages":"82"},"PeriodicalIF":7.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152590","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}