Pub Date : 2025-08-28DOI: 10.1186/s13293-025-00745-0
Amy E Chan, Gillian S Driscoll, Zaynah Usmani, Angela R Ozburn
Background: Women tend to progress from initial alcohol use to dependence more rapidly than men, a phenomenon known as the "telescoping effect". This suggests different consequences of early alcohol use, which can impact the development of an Alcohol Use Disorder (AUD). Previous evidence demonstrated that nucleus accumbens core (NAcC) chemogenetic manipulations resulted in opposite effects on binge-like drinking [stimulation decreased ethanol intake in C57BL/6J (B6) females, while inhibition decreased intake in males]. In humans, ethanol cue conditioning is linked to the positive subjective effects of alcohol intake and intoxication. We tested the hypothesis that chemogenetic manipulation of NAcC activity alters ethanol reward (measured by conditioned place preference, CPP) in a sex-specific manner.
Methods: In Experiment 1, surgery naïve B6 mice (n = 11-12/sex/treatment) underwent an ethanol CPP protocol and were administered the Designer Receptors Exclusively Activated by Designer Drugs (DREADD) actuator clozapine-N-oxide (CNO, 1 mg/kg) or vehicle prior to ethanol (2 g/kg) conditioning. In Experiment 2, B6 mice underwent surgery to deliver control (mCherry), excitatory (hM3Dq), or inhibitory (hM4Di) DREADDs to the NAcC (n = 8-13/sex/treatment). After recovery, mice underwent ethanol CPP as in Experiment 1. CPP was conducted in a 3-chamber apparatus. Time spent in each chamber was recorded during the pre-test (before conditioning), and the test (after 4 ethanol and 4 saline conditioning sessions). Data were analyzed separately by sex, viral condition, and treatment with a 2-way RM ANOVA [factors: Time (repeated measure), Chamber].
Results: Both surgery naïve (Experiment 1) and mCherry-expressing female and male B6 mice condition similarly to an intoxicating dose of ethanol and CNO did not interfere with ethanol CPP in the absence of DREADDs. Experiment 2 revealed that NAcC chemogenetic stimulation prevented ethanol CPP in males, while NAcC chemogenetic inhibition prevented ethanol CPP in females.
Conclusions: NAcC chemogenetic manipulations alter ethanol reward differently in male and female B6 mice. Together with prior work, we demonstrate that NAcC activity has a sex-specific role during ethanol reward and consumption. Evidence of sex differences in ethanol reward may help future research to uncover the mechanisms underlying the "telescoping effect" and why women have an increased risk for developing an AUD.
{"title":"Nucleus accumbens core chemogenetic excitation in male mice and chemogenetic inhibition in female mice reduced ethanol reward.","authors":"Amy E Chan, Gillian S Driscoll, Zaynah Usmani, Angela R Ozburn","doi":"10.1186/s13293-025-00745-0","DOIUrl":"https://doi.org/10.1186/s13293-025-00745-0","url":null,"abstract":"<p><strong>Background: </strong>Women tend to progress from initial alcohol use to dependence more rapidly than men, a phenomenon known as the \"telescoping effect\". This suggests different consequences of early alcohol use, which can impact the development of an Alcohol Use Disorder (AUD). Previous evidence demonstrated that nucleus accumbens core (NAcC) chemogenetic manipulations resulted in opposite effects on binge-like drinking [stimulation decreased ethanol intake in C57BL/6J (B6) females, while inhibition decreased intake in males]. In humans, ethanol cue conditioning is linked to the positive subjective effects of alcohol intake and intoxication. We tested the hypothesis that chemogenetic manipulation of NAcC activity alters ethanol reward (measured by conditioned place preference, CPP) in a sex-specific manner.</p><p><strong>Methods: </strong>In Experiment 1, surgery naïve B6 mice (n = 11-12/sex/treatment) underwent an ethanol CPP protocol and were administered the Designer Receptors Exclusively Activated by Designer Drugs (DREADD) actuator clozapine-N-oxide (CNO, 1 mg/kg) or vehicle prior to ethanol (2 g/kg) conditioning. In Experiment 2, B6 mice underwent surgery to deliver control (mCherry), excitatory (hM3Dq), or inhibitory (hM4Di) DREADDs to the NAcC (n = 8-13/sex/treatment). After recovery, mice underwent ethanol CPP as in Experiment 1. CPP was conducted in a 3-chamber apparatus. Time spent in each chamber was recorded during the pre-test (before conditioning), and the test (after 4 ethanol and 4 saline conditioning sessions). Data were analyzed separately by sex, viral condition, and treatment with a 2-way RM ANOVA [factors: Time (repeated measure), Chamber].</p><p><strong>Results: </strong>Both surgery naïve (Experiment 1) and mCherry-expressing female and male B6 mice condition similarly to an intoxicating dose of ethanol and CNO did not interfere with ethanol CPP in the absence of DREADDs. Experiment 2 revealed that NAcC chemogenetic stimulation prevented ethanol CPP in males, while NAcC chemogenetic inhibition prevented ethanol CPP in females.</p><p><strong>Conclusions: </strong>NAcC chemogenetic manipulations alter ethanol reward differently in male and female B6 mice. Together with prior work, we demonstrate that NAcC activity has a sex-specific role during ethanol reward and consumption. Evidence of sex differences in ethanol reward may help future research to uncover the mechanisms underlying the \"telescoping effect\" and why women have an increased risk for developing an AUD.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"66"},"PeriodicalIF":5.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940954","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}
Pub Date : 2025-08-25DOI: 10.1186/s13293-025-00746-z
Zsófia Ruppert, Márta Sárközy, Bettina Rákóczi, Brigitta Dukay, Petra Hajdu, Gergő Szűcs, Zsolt Galla, Ákos Hunya, Ferenc Kovács, András Kriston, Péter Monostori, Péter Horváth, Gábor Cserni, László Tiszlavicz, Tamás Csont, László Vígh, Miklós Sántha, Zsolt Török, Melinda E Tóth
Background: Obesity is a global health challenge that can lead to various complications, such as metabolic syndrome, diabetes mellitus, and cardiovascular diseases. Heat shock proteins are evolutionarily conserved chaperones that help maintain cellular protein homeostasis. Their expression is dysregulated in various chronic diseases, including diabetes mellitus and hyperlipidemia, and they also regulate inflammatory processes. Therefore, the present study aimed to investigate the effects of a small heat shock protein, HSPB1, on the comorbidities and complications of obesity in a transgenic mouse model.
Methods: Male and female human apolipoprotein B-100 (APOB) transgenic mice fed with a high-fat diet (HFD) from months 3-10 of age were used as a model of metabolic syndrome (MetS). To study whether HSPB1 influences the development of MetS, APOB animals were crossed with HSPB1-overexpressing mice. Age and sex-matched wild-type and human HSPB1-overexpressing mice were used as controls. Changes in cardiac morphology and function were assessed by transthoracic echocardiography at month 9. At month 10, serum triglyceride and cholesterol concentrations were determined by enzymatic colorimetric assays. Pathological changes in the liver were studied on hematoxylin-eosin-stained sections. Expression levels of genes involved in inflammation and metabolism were measured by quantitative real-time polymerase chain reaction in the liver, left ventricle, and visceral white adipose tissue (vWAT).
Results: The body weight and serum LDL-cholesterol levels were significantly higher in the APOB animals than in the wild-type mice in both sexes. Notably, HSPB1 overexpression further increased weight gain in female APOB animals. Conversely, in APOB males, HSPB1 overexpression decreased LDL-cholesterol levels without significantly affecting body weight. Furthermore, in APOB females, HSPB1 overexpression elevated Fgf-21 expression in the vWAT, restored Lpl levels, and reduced the expression of several cytokines in the liver. APOB males developed left ventricular hypertrophy (LVH) with diastolic dysfunction. HSPB1 overexpression induced LVH without cardiac dysfunction in the wild-type animals.
Conclusions: Both sexes of APOB animals developed MetS. APOB males presented LVH with preserved ejection fraction (EF); however, APOB females showed enlarged left ventricular end-systolic volume (LVESV). In APOB animals, HSPB1 overexpression exerted a sex-dependent influence on obesity-related alterations, including weight gain, hypercholesterolemia, and hepatic and vWAT gene expression.
{"title":"Overexpression of the human heat shock protein B1 alters obesity-related metabolic changes in a sex-dependent manner in a mouse model of metabolic syndrome.","authors":"Zsófia Ruppert, Márta Sárközy, Bettina Rákóczi, Brigitta Dukay, Petra Hajdu, Gergő Szűcs, Zsolt Galla, Ákos Hunya, Ferenc Kovács, András Kriston, Péter Monostori, Péter Horváth, Gábor Cserni, László Tiszlavicz, Tamás Csont, László Vígh, Miklós Sántha, Zsolt Török, Melinda E Tóth","doi":"10.1186/s13293-025-00746-z","DOIUrl":"https://doi.org/10.1186/s13293-025-00746-z","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a global health challenge that can lead to various complications, such as metabolic syndrome, diabetes mellitus, and cardiovascular diseases. Heat shock proteins are evolutionarily conserved chaperones that help maintain cellular protein homeostasis. Their expression is dysregulated in various chronic diseases, including diabetes mellitus and hyperlipidemia, and they also regulate inflammatory processes. Therefore, the present study aimed to investigate the effects of a small heat shock protein, HSPB1, on the comorbidities and complications of obesity in a transgenic mouse model.</p><p><strong>Methods: </strong>Male and female human apolipoprotein B-100 (APOB) transgenic mice fed with a high-fat diet (HFD) from months 3-10 of age were used as a model of metabolic syndrome (MetS). To study whether HSPB1 influences the development of MetS, APOB animals were crossed with HSPB1-overexpressing mice. Age and sex-matched wild-type and human HSPB1-overexpressing mice were used as controls. Changes in cardiac morphology and function were assessed by transthoracic echocardiography at month 9. At month 10, serum triglyceride and cholesterol concentrations were determined by enzymatic colorimetric assays. Pathological changes in the liver were studied on hematoxylin-eosin-stained sections. Expression levels of genes involved in inflammation and metabolism were measured by quantitative real-time polymerase chain reaction in the liver, left ventricle, and visceral white adipose tissue (vWAT).</p><p><strong>Results: </strong>The body weight and serum LDL-cholesterol levels were significantly higher in the APOB animals than in the wild-type mice in both sexes. Notably, HSPB1 overexpression further increased weight gain in female APOB animals. Conversely, in APOB males, HSPB1 overexpression decreased LDL-cholesterol levels without significantly affecting body weight. Furthermore, in APOB females, HSPB1 overexpression elevated Fgf-21 expression in the vWAT, restored Lpl levels, and reduced the expression of several cytokines in the liver. APOB males developed left ventricular hypertrophy (LVH) with diastolic dysfunction. HSPB1 overexpression induced LVH without cardiac dysfunction in the wild-type animals.</p><p><strong>Conclusions: </strong>Both sexes of APOB animals developed MetS. APOB males presented LVH with preserved ejection fraction (EF); however, APOB females showed enlarged left ventricular end-systolic volume (LVESV). In APOB animals, HSPB1 overexpression exerted a sex-dependent influence on obesity-related alterations, including weight gain, hypercholesterolemia, and hepatic and vWAT gene expression.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"65"},"PeriodicalIF":5.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940950","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}
Pub Date : 2025-08-19DOI: 10.1186/s13293-025-00747-y
Lara A Coelho, Daniela E Aguilar Ramirez, Serena Basta, Marta Guarischi, Claudia L R Gonzalez, Monica Gori
<p><p>There is contradictory evidence on the effect that visual experience has on haptic abilities. Indeed, some studies have documented that a lack of vision (blindness) results in decreased haptic perception, whereas other studies report an enhanced haptic ability in blind individuals. To examine the role of vision in haptic spatial processing, we recruited early blind, late blind, and sighted participants. Each participant completed a haptic task in which they explored a two-piece LEGO model for eight seconds before searching for the same pieces in a bowl of distractors. Our results showed that blind individuals made more errors than sighted participants. Furthermore, early blind participants performed worse than both late blind and sighted participants, who performed similarly. These findings highlight the importance that vision plays in the development of accurate haptic spatial perception. Additionally, we investigated whether the commonly reported male advantage in haptic tasks depends on visual experience. Our results showed better performance by males in all groups when compared to females. This result suggests that sex differences in haptic spatial processing are a fundamental characteristic of human sensory function, independent of visual experience.Highlights No study has investigated if the previously identified male advantage in haptic spatial processing is mediated by visual experience. Blind participants made more errors than sighted participants; early blind performed the worst. The findings suggest vision is crucial for the development of accurate haptic spatial perception. There was a consistent male advantage in haptic performance across all visual experience groups. Sex differences in haptic spatial ability appear to be independent of visual expertise. Plain language summarySome researchers have suggested that being blind reduces abilities in their other senses, while others believe that a lack of vision can improve them. To further understand which is true, we investigated whether the haptic system-the combination of touch and proprioception (awareness of where the body is in space)-is affected by blindness. To do this, we tested people who were blind from birth (early blind), people who became blind later in life (late blind), and people who can see (sighted) on a simple haptic task. In the task, participants felt a small LEGO model with their hands for eight seconds. Then, they had to find the same LEGO pieces in a bowl filled with other, distractor pieces-using only haptics. We found that blind participants made more mistakes than sighted participants. Those who were blind from birth had the most difficulty. People who became blind later in life performed similarly to sighted individuals. This suggests that vision plays an important role in developing accurate haptic perception. As previous work has shown that males outperform females on haptic tasks, we also investigated whether those differences depended on vision. We f
{"title":"The role of visual experience in haptic spatial perception: evidence from early blind, late blind, and sighted individuals.","authors":"Lara A Coelho, Daniela E Aguilar Ramirez, Serena Basta, Marta Guarischi, Claudia L R Gonzalez, Monica Gori","doi":"10.1186/s13293-025-00747-y","DOIUrl":"10.1186/s13293-025-00747-y","url":null,"abstract":"<p><p>There is contradictory evidence on the effect that visual experience has on haptic abilities. Indeed, some studies have documented that a lack of vision (blindness) results in decreased haptic perception, whereas other studies report an enhanced haptic ability in blind individuals. To examine the role of vision in haptic spatial processing, we recruited early blind, late blind, and sighted participants. Each participant completed a haptic task in which they explored a two-piece LEGO model for eight seconds before searching for the same pieces in a bowl of distractors. Our results showed that blind individuals made more errors than sighted participants. Furthermore, early blind participants performed worse than both late blind and sighted participants, who performed similarly. These findings highlight the importance that vision plays in the development of accurate haptic spatial perception. Additionally, we investigated whether the commonly reported male advantage in haptic tasks depends on visual experience. Our results showed better performance by males in all groups when compared to females. This result suggests that sex differences in haptic spatial processing are a fundamental characteristic of human sensory function, independent of visual experience.Highlights No study has investigated if the previously identified male advantage in haptic spatial processing is mediated by visual experience. Blind participants made more errors than sighted participants; early blind performed the worst. The findings suggest vision is crucial for the development of accurate haptic spatial perception. There was a consistent male advantage in haptic performance across all visual experience groups. Sex differences in haptic spatial ability appear to be independent of visual expertise. Plain language summarySome researchers have suggested that being blind reduces abilities in their other senses, while others believe that a lack of vision can improve them. To further understand which is true, we investigated whether the haptic system-the combination of touch and proprioception (awareness of where the body is in space)-is affected by blindness. To do this, we tested people who were blind from birth (early blind), people who became blind later in life (late blind), and people who can see (sighted) on a simple haptic task. In the task, participants felt a small LEGO model with their hands for eight seconds. Then, they had to find the same LEGO pieces in a bowl filled with other, distractor pieces-using only haptics. We found that blind participants made more mistakes than sighted participants. Those who were blind from birth had the most difficulty. People who became blind later in life performed similarly to sighted individuals. This suggests that vision plays an important role in developing accurate haptic perception. As previous work has shown that males outperform females on haptic tasks, we also investigated whether those differences depended on vision. We f","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"64"},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881982","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}
Pub Date : 2025-08-11DOI: 10.1186/s13293-025-00740-5
Marlo Vernon, Brianna McIndoe, Michael J Ryan, Amanda Behr, Daria Ilatovskaya, Ananya Chakraborty, Suma Yellamraju, Ara Idun, Jennifer Sullivan
Background and aims: In the United States, cardiovascular disease (CVD) is the leading cause of death among both men and women; CVD and associated risk factors particularly affect women who live in rural areas. This mixed-methods analysis aims to explore cardiovascular health (CVH) risk factors and healthcare experiences among women in rural Georgia, to identify barriers to care, and to inform strategies for improving long-term health outcomes in rural communities.
Methods: A convergent mixed methods design was utilized to evaluate CVH prevalence and associated environmental risk factors among women living in rural GA. Quantitative data from 159 Georgia counties were analyzed to compare rural and urban rates of CVD-related conditions and healthcare provider availability. Comparative analyses were performed between counties, urban and rural areas, and on sex differences. Concurrently, semi-structured interviews were conducted with 56 women and 11 healthcare providers to explore knowledge of blood pressure (BP) management, access to preventive services, and barriers to care. Qualitative and quantitative findings were analyzed separately and integrated during interpretation.
Results: Rural counties have significantly higher prevalence of hypertension, obesity and stroke. General trends revealed higher rates of smoking, physical inactivity, and excessive alcohol consumption in rural counties compared to rates in urban counties of GA. Qualitative themes revealed affordability concerns, communication challenges between patients and providers, limited trust in telehealth, and the importance of delivering CVH education in community-based settings. Differences by age were also observed: younger women expressed less concern or awareness about CVH risks, while older women described greater engagement with care and health information. While the original aim included gaps in awareness and education, participants primarily described navigating systemic barriers across the care continuum.
Conclusion: Rural women face individual, provider, and structural barriers to cardiovascular health and care. This unique study identifies chronic disease disparities and risk factors, with a higher disease burden observed in rural counties. Contributing factors may include limited resources for promoting healthy lifestyle choices, and reduced access to healthcare providers. Integrated findings underscore the need for sex- and gender- informed, age-specific, and community tailored strategies that address both health system access, and communication to improve CVH outcomes in underserved rural populations.
{"title":"A comprehensive mixed-methods analysis of women's cardiovascular health needs in Georgia, United States.","authors":"Marlo Vernon, Brianna McIndoe, Michael J Ryan, Amanda Behr, Daria Ilatovskaya, Ananya Chakraborty, Suma Yellamraju, Ara Idun, Jennifer Sullivan","doi":"10.1186/s13293-025-00740-5","DOIUrl":"10.1186/s13293-025-00740-5","url":null,"abstract":"<p><strong>Background and aims: </strong>In the United States, cardiovascular disease (CVD) is the leading cause of death among both men and women; CVD and associated risk factors particularly affect women who live in rural areas. This mixed-methods analysis aims to explore cardiovascular health (CVH) risk factors and healthcare experiences among women in rural Georgia, to identify barriers to care, and to inform strategies for improving long-term health outcomes in rural communities.</p><p><strong>Methods: </strong>A convergent mixed methods design was utilized to evaluate CVH prevalence and associated environmental risk factors among women living in rural GA. Quantitative data from 159 Georgia counties were analyzed to compare rural and urban rates of CVD-related conditions and healthcare provider availability. Comparative analyses were performed between counties, urban and rural areas, and on sex differences. Concurrently, semi-structured interviews were conducted with 56 women and 11 healthcare providers to explore knowledge of blood pressure (BP) management, access to preventive services, and barriers to care. Qualitative and quantitative findings were analyzed separately and integrated during interpretation.</p><p><strong>Results: </strong>Rural counties have significantly higher prevalence of hypertension, obesity and stroke. General trends revealed higher rates of smoking, physical inactivity, and excessive alcohol consumption in rural counties compared to rates in urban counties of GA. Qualitative themes revealed affordability concerns, communication challenges between patients and providers, limited trust in telehealth, and the importance of delivering CVH education in community-based settings. Differences by age were also observed: younger women expressed less concern or awareness about CVH risks, while older women described greater engagement with care and health information. While the original aim included gaps in awareness and education, participants primarily described navigating systemic barriers across the care continuum.</p><p><strong>Conclusion: </strong>Rural women face individual, provider, and structural barriers to cardiovascular health and care. This unique study identifies chronic disease disparities and risk factors, with a higher disease burden observed in rural counties. Contributing factors may include limited resources for promoting healthy lifestyle choices, and reduced access to healthcare providers. Integrated findings underscore the need for sex- and gender- informed, age-specific, and community tailored strategies that address both health system access, and communication to improve CVH outcomes in underserved rural populations.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"62"},"PeriodicalIF":5.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820381","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}
Pub Date : 2025-08-11DOI: 10.1186/s13293-025-00739-y
Lisa A Kilpatrick, Lin Chang, Jennifer S Labus, Andrea S Shin, Michelle Choy, Tien S Dong, Bruce Naliboff, Emeran A Mayer, Arpana Church
Background: Irritable bowel syndrome (IBS) is a stress-sensitive disorder that exhibits sex differences in brain-gut-microbiome interactions. Neighborhood disadvantage is a chronic stressor that may influence brain-gut-microbiome health in patients with IBS, potentially contributing to clinical profiles in a sex-specific manner. This study evaluated sex-based associations between neighborhood disadvantage and clinical characteristics, cortical morphology, and Prevotella relative abundance (a sex-specific microbial marker in IBS) in individuals with IBS compared to healthy controls (HCs).
Methods: Brain magnetic resonance imaging scans were obtained in 182 individuals with IBS (age, 31.0 ± 0.8 years; 128 females) and 161 HCs (age, 32.7 ± 1.0 years; 94 females). Fecal microbiome data was available in 113 IBS participants (80 females) and 127 HCs (74 females). Current neighborhood disadvantage was assessed as the Area Deprivation Index (ADI), with ADI⩾5 defined as high ADI. Group differences in the associations of high ADI with symptoms, Prevotella, and cortical morphology were evaluated using partial least squares.
Results: Diagnosis Differences: High ADI was associated with greater lateral intraparietal surface area in IBS vs HCs. Sex Differences: There were greater negative associations between high ADI and surface area in frontal operculum and thickness in frontopolar and primary somatosensory regions in females vs males. Diagnosis*Sex Differences: There were greater negative associations between high ADI and surface area in superior parietal and sensorimotor regions in IBS females vs males, and greater negative associations between high ADI and surface area and thickness in dorsolateral prefrontal and parietal regions, respectively, in IBS males vs females. High ADI was associated with greater symptom severity in IBS males, greater perceived stress in both IBS and HC females, and Prevotella relative abundance in IBS females (all p's < 0.01).
Conclusions: Neighborhood disadvantage is associated with greater symptom severity in IBS males and both higher perceived stress (exacerbates symptoms) and Prevotella abundance (protective) in IBS females. It generally has a greater negative impact on emotion/pain-related cortical morphology in females vs males. However, there are more prominent somatosensory reductions in IBS females, and prefrontal reductions in IBS males. These findings highlight the interplay between social and biological factors in IBS and underscore the need for targeted, sex-specific interventions.
{"title":"Sex-based associations between neighborhood disadvantage and brain-gut alterations in individuals with irritable bowel syndrome.","authors":"Lisa A Kilpatrick, Lin Chang, Jennifer S Labus, Andrea S Shin, Michelle Choy, Tien S Dong, Bruce Naliboff, Emeran A Mayer, Arpana Church","doi":"10.1186/s13293-025-00739-y","DOIUrl":"10.1186/s13293-025-00739-y","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome (IBS) is a stress-sensitive disorder that exhibits sex differences in brain-gut-microbiome interactions. Neighborhood disadvantage is a chronic stressor that may influence brain-gut-microbiome health in patients with IBS, potentially contributing to clinical profiles in a sex-specific manner. This study evaluated sex-based associations between neighborhood disadvantage and clinical characteristics, cortical morphology, and Prevotella relative abundance (a sex-specific microbial marker in IBS) in individuals with IBS compared to healthy controls (HCs).</p><p><strong>Methods: </strong>Brain magnetic resonance imaging scans were obtained in 182 individuals with IBS (age, 31.0 ± 0.8 years; 128 females) and 161 HCs (age, 32.7 ± 1.0 years; 94 females). Fecal microbiome data was available in 113 IBS participants (80 females) and 127 HCs (74 females). Current neighborhood disadvantage was assessed as the Area Deprivation Index (ADI), with ADI⩾5 defined as high ADI. Group differences in the associations of high ADI with symptoms, Prevotella, and cortical morphology were evaluated using partial least squares.</p><p><strong>Results: </strong>Diagnosis Differences: High ADI was associated with greater lateral intraparietal surface area in IBS vs HCs. Sex Differences: There were greater negative associations between high ADI and surface area in frontal operculum and thickness in frontopolar and primary somatosensory regions in females vs males. Diagnosis*Sex Differences: There were greater negative associations between high ADI and surface area in superior parietal and sensorimotor regions in IBS females vs males, and greater negative associations between high ADI and surface area and thickness in dorsolateral prefrontal and parietal regions, respectively, in IBS males vs females. High ADI was associated with greater symptom severity in IBS males, greater perceived stress in both IBS and HC females, and Prevotella relative abundance in IBS females (all p's < 0.01).</p><p><strong>Conclusions: </strong>Neighborhood disadvantage is associated with greater symptom severity in IBS males and both higher perceived stress (exacerbates symptoms) and Prevotella abundance (protective) in IBS females. It generally has a greater negative impact on emotion/pain-related cortical morphology in females vs males. However, there are more prominent somatosensory reductions in IBS females, and prefrontal reductions in IBS males. These findings highlight the interplay between social and biological factors in IBS and underscore the need for targeted, sex-specific interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"61"},"PeriodicalIF":5.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820382","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}
Pub Date : 2025-08-06DOI: 10.1186/s13293-025-00743-2
Laila A Chaudhry, Yasmine Coovadia, Brittany K Schwende, Danielle E Berbrier, Will Huckins, Jinan Saboune, Derek A Skolnik, Emily K Van Berkel, Jeffrey S Mogil, Charlotte W Usselman
Background: Chronic pain is partly maintained by the sympathetic nervous system, whose activity is best measured by muscle sympathetic nerve activity (MSNA). MSNA responses to acute pain have been thoroughly investigated, whereas MSNA responses to longer-lasting pain are poorly understood. Therefore, this study examined the relationship between pain ratings and peroneal MSNA during a tonic cold pressor test (CPT) in male and female participants.
Methods: We obtained MSNA measures during a 6 min CPT in 18 young adult (20-33 years) men and women. Verbal pain ratings (0-10) and autonomic outcomes (heart rate [HR], mean arterial blood pressure [MAP], and MSNA) were assessed simultaneously at multiple time points across the CPT.
Results: Pain, HR, and MAP increased in the initial 30s in both sexes. Females increased their MSNA burst frequency (BF) to a greater extent than males. Across the full CPT we observed a positive relationship between pain and HR in males, a positive relationship between pain and MSNA BF in females, and a negative relationship between pain and MSNA burst amplitude in females.
Conclusions: Overall, males displayed a strong relationship between tonic pain and HR, an index of parasympathetic activity, whereas females displayed strong and offsetting relationships between tonic pain and purely sympathetic MSNA variables. These observations suggest sex differences in autonomic mechanisms during tonic pain, which may have relevance to ongoing efforts to modulate pain via manipulations of the autonomic nervous system, as well as sex/gender disparities in chronic pain prevalence.
{"title":"Sex differences in the relationship between pain and autonomic outflow during a cold pressor test.","authors":"Laila A Chaudhry, Yasmine Coovadia, Brittany K Schwende, Danielle E Berbrier, Will Huckins, Jinan Saboune, Derek A Skolnik, Emily K Van Berkel, Jeffrey S Mogil, Charlotte W Usselman","doi":"10.1186/s13293-025-00743-2","DOIUrl":"10.1186/s13293-025-00743-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is partly maintained by the sympathetic nervous system, whose activity is best measured by muscle sympathetic nerve activity (MSNA). MSNA responses to acute pain have been thoroughly investigated, whereas MSNA responses to longer-lasting pain are poorly understood. Therefore, this study examined the relationship between pain ratings and peroneal MSNA during a tonic cold pressor test (CPT) in male and female participants.</p><p><strong>Methods: </strong>We obtained MSNA measures during a 6 min CPT in 18 young adult (20-33 years) men and women. Verbal pain ratings (0-10) and autonomic outcomes (heart rate [HR], mean arterial blood pressure [MAP], and MSNA) were assessed simultaneously at multiple time points across the CPT.</p><p><strong>Results: </strong>Pain, HR, and MAP increased in the initial 30s in both sexes. Females increased their MSNA burst frequency (BF) to a greater extent than males. Across the full CPT we observed a positive relationship between pain and HR in males, a positive relationship between pain and MSNA BF in females, and a negative relationship between pain and MSNA burst amplitude in females.</p><p><strong>Conclusions: </strong>Overall, males displayed a strong relationship between tonic pain and HR, an index of parasympathetic activity, whereas females displayed strong and offsetting relationships between tonic pain and purely sympathetic MSNA variables. These observations suggest sex differences in autonomic mechanisms during tonic pain, which may have relevance to ongoing efforts to modulate pain via manipulations of the autonomic nervous system, as well as sex/gender disparities in chronic pain prevalence.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"60"},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793384","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}
Pub Date : 2025-08-06DOI: 10.1186/s13293-025-00742-3
Bethany G Beekly, Dania Zeidan, Wenicios F Chaves, Jonah-Isabella Sta-Monica, Thomas Saunders, Cristina Saenz de Miera, Christian R Burgess, Carol F Elias
{"title":"Lack of glutamate neurotransmission in melanin-concentrating hormone neurons alters mouse reproduction and metabolism in a sex-specific manner.","authors":"Bethany G Beekly, Dania Zeidan, Wenicios F Chaves, Jonah-Isabella Sta-Monica, Thomas Saunders, Cristina Saenz de Miera, Christian R Burgess, Carol F Elias","doi":"10.1186/s13293-025-00742-3","DOIUrl":"10.1186/s13293-025-00742-3","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"59"},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793383","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}
Pub Date : 2025-08-04DOI: 10.1186/s13293-025-00741-4
Candice L Malone, Jiaxuan Li, Elsa M Luebke, Leykza Carreras-Simons, Warren W Treis, Emma R Hammond, Patrick K Monari, Catherine A Marler
The monogamous California mouse (Peromyscus californicus) exhibits distinct behavioral changes during pair bond formation. Using a detailed temporal behavioral analysis over seven days, we found a rapid decrease in aggression within 24 h of pair introduction in this highly territorial species. After this aggression reduction, the gradual increase in affiliative behaviors varied by type of affiliative behavior and ranged from one to seven days. We then measured neurobiological changes at three time points during this transition to uncover mechanisms that might govern this shift from aggressive to affiliative behavior, revealing novel sex differences that add to current research on biological mechanisms of social bonding. Specifically, we examined plasticity through mRNA expression of two perineuronal net (PNN) associated proteins, HAPLN and ACAN, in two brain regions implicated in affiliation, aggression, and social cognition: the ventral anterior cingulate cortex (vACC) and lateral septum (LS). The vACC in females exhibited higher expression levels of both of these PNN components relative to males. Additionally, we observed a decrease in ACAN mRNA expression in the vACC over the course of pair bond establishment, but no such change in the LS. Furthermore, oxytocin receptor (OXTR) and vasopressin receptor (AVPR) plasticity exhibited sex-specific patterns in the vACC during pair bond formation. Females displayed higher OXTR mRNA expression across the bonding period, whereas males expressed higher AVPR mRNA levels. We discuss how a decrease in PNNs could allow for an increase in receptor plasticity in the vACC as the pair bond is established. Moreover, we suggest that structural plasticity across this social transition may differ between males and females due to factors such as pre-pair sociality and aggression/territoriality changes.
{"title":"Sex differences in structural and receptor mRNA expression in the ventral anterior cingulate cortex and a potential role of perineuronal nets in monogamous pair bond establishment (Peromyscus californicus).","authors":"Candice L Malone, Jiaxuan Li, Elsa M Luebke, Leykza Carreras-Simons, Warren W Treis, Emma R Hammond, Patrick K Monari, Catherine A Marler","doi":"10.1186/s13293-025-00741-4","DOIUrl":"10.1186/s13293-025-00741-4","url":null,"abstract":"<p><p>The monogamous California mouse (Peromyscus californicus) exhibits distinct behavioral changes during pair bond formation. Using a detailed temporal behavioral analysis over seven days, we found a rapid decrease in aggression within 24 h of pair introduction in this highly territorial species. After this aggression reduction, the gradual increase in affiliative behaviors varied by type of affiliative behavior and ranged from one to seven days. We then measured neurobiological changes at three time points during this transition to uncover mechanisms that might govern this shift from aggressive to affiliative behavior, revealing novel sex differences that add to current research on biological mechanisms of social bonding. Specifically, we examined plasticity through mRNA expression of two perineuronal net (PNN) associated proteins, HAPLN and ACAN, in two brain regions implicated in affiliation, aggression, and social cognition: the ventral anterior cingulate cortex (vACC) and lateral septum (LS). The vACC in females exhibited higher expression levels of both of these PNN components relative to males. Additionally, we observed a decrease in ACAN mRNA expression in the vACC over the course of pair bond establishment, but no such change in the LS. Furthermore, oxytocin receptor (OXTR) and vasopressin receptor (AVPR) plasticity exhibited sex-specific patterns in the vACC during pair bond formation. Females displayed higher OXTR mRNA expression across the bonding period, whereas males expressed higher AVPR mRNA levels. We discuss how a decrease in PNNs could allow for an increase in receptor plasticity in the vACC as the pair bond is established. Moreover, we suggest that structural plasticity across this social transition may differ between males and females due to factors such as pre-pair sociality and aggression/territoriality changes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"58"},"PeriodicalIF":5.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783396","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}
Pub Date : 2025-07-25DOI: 10.1186/s13293-025-00738-z
Leah A Holcomb, Elizabeth Crabtree Killen, Kelsey R Ryan, Aimee L McRae-Clark, Stacey Seipel, Rita Aidoo, Constance Guille
Background: Social drivers of health (SDOH) significantly influence health behaviors and outcomes, yet sex-based disparities in these domains remain underexplored. Identifying these differences is essential for guiding equitable, evidence-based interventions.
Methods: We analyzed electronic health record (EHR) data from all patients with a documented male or female sex who had a primary care visit or inpatient stay at the Medical University of South Carolina (MUSC) between January 1, 2023, and December 31, 2024 (n = 493,920). SDOH screening responses were categorized as "affirmative" (at risk) or "negative" (not at risk) across 17 predefined domains using Epic's logic-based risk classification. Descriptive statistics were calculated, and z-tests for proportions were used to assess sex-based differences. Race and ethnicity were included as descriptive variables; no inferential tests by race/ethnicity were conducted.
Results: Females were significantly more likely to report financial strain (7.96%), food insecurity (4.44%), housing instability (3.72%), intimate partner violence (2.03%), transportation barriers (2.20%), depression (3.93%), and stress (14.10%). Despite these risks, females also reported higher rates of protective behaviors such as physical activity (74.2%) and social connectedness (14.22%). In contrast, males had higher rates of alcohol use (4.67%), tobacco use (35.6%), and adolescent substance use (2.14%). Notably, White/Caucasian males reported the highest alcohol use (6.23%), and both White and Black males reported the highest tobacco use (42%).
Conclusions: Sex-based disparities in SDOH reflect broader structural and social inequities. Health systems should implement routine, EHR-integrated SDOH screening and use this data to inform tailored, gender-responsive interventions-such as increasing access to mental health support for women and addressing substance use among men-while also considering how intersecting factors like race, income, and caregiving burden compound these risks.
{"title":"A comparison of social drivers of health identification and intervention rates by sex among patients receiving primary care.","authors":"Leah A Holcomb, Elizabeth Crabtree Killen, Kelsey R Ryan, Aimee L McRae-Clark, Stacey Seipel, Rita Aidoo, Constance Guille","doi":"10.1186/s13293-025-00738-z","DOIUrl":"10.1186/s13293-025-00738-z","url":null,"abstract":"<p><strong>Background: </strong>Social drivers of health (SDOH) significantly influence health behaviors and outcomes, yet sex-based disparities in these domains remain underexplored. Identifying these differences is essential for guiding equitable, evidence-based interventions.</p><p><strong>Methods: </strong>We analyzed electronic health record (EHR) data from all patients with a documented male or female sex who had a primary care visit or inpatient stay at the Medical University of South Carolina (MUSC) between January 1, 2023, and December 31, 2024 (n = 493,920). SDOH screening responses were categorized as \"affirmative\" (at risk) or \"negative\" (not at risk) across 17 predefined domains using Epic's logic-based risk classification. Descriptive statistics were calculated, and z-tests for proportions were used to assess sex-based differences. Race and ethnicity were included as descriptive variables; no inferential tests by race/ethnicity were conducted.</p><p><strong>Results: </strong>Females were significantly more likely to report financial strain (7.96%), food insecurity (4.44%), housing instability (3.72%), intimate partner violence (2.03%), transportation barriers (2.20%), depression (3.93%), and stress (14.10%). Despite these risks, females also reported higher rates of protective behaviors such as physical activity (74.2%) and social connectedness (14.22%). In contrast, males had higher rates of alcohol use (4.67%), tobacco use (35.6%), and adolescent substance use (2.14%). Notably, White/Caucasian males reported the highest alcohol use (6.23%), and both White and Black males reported the highest tobacco use (42%).</p><p><strong>Conclusions: </strong>Sex-based disparities in SDOH reflect broader structural and social inequities. Health systems should implement routine, EHR-integrated SDOH screening and use this data to inform tailored, gender-responsive interventions-such as increasing access to mental health support for women and addressing substance use among men-while also considering how intersecting factors like race, income, and caregiving burden compound these risks.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"57"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717304","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}
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