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1.
PLoS One ; 19(7): e0306661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008488

RESUMO

OBJECTIVE: The aim of this study was to investigate the association between sleep duration and muscle quality index (MQI) in middle-aged and older age groups, as limited evidence exists on this topic. METHODS: In order to assess the relationship between sleep duration and MQI, a cross-sectional study was undertaken, utilizing data from the National Health and Nutrition Examination Survey (NHANES) acquired during the period from 2011 to 2014. The study comprised a total of 4598 participants aged 20 years and above. To examine the association between sleep duration and MQI, sophisticated weighted multivariate linear regression models were employed. Additionally, smooth curve fitting techniques were applied to examine the possibility of any non-linear relationship between the two variables. RESULTS: The average age of the adults who were enrolled in the study was 38.48±11.69 years, and 46.75% of them were female. The results of the multivariable linear regression models showed that sleep duration had a positive correlation with MQI. However, when subgroup analysis was conducted, it was found that this positive correlation only existed among women (ß = 0.09, 95% CI: 0.014 to 0.167). To further confirm the differences between sexes in the relationship between sleep duration and MQI, a weighted generalized additive model (GAM) was used. CONCLUSIONS: This research study provides evidence that there is a positive correlation between the duration of sleep and MQI specifically in females, while no such association was observed in males. These findings shed light on the existence of gender disparities in the connection between sleep duration and MQI.


Assuntos
Inquéritos Nutricionais , Sono , Humanos , Feminino , Masculino , Adulto , Estudos Transversais , Sono/fisiologia , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem , Idoso , Caracteres Sexuais , Músculo Esquelético/fisiologia , Fatores de Tempo , Modelos Lineares , Duração do Sono
2.
Biol Sex Differ ; 15(1): 55, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010139

RESUMO

BACKGROUND: Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice. METHODS: To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis. RESULTS: We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress. CONCLUSIONS: Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.


In our study, we attempted to investigate how the combination of diet, stress, and sex can affect various aspects of health in mice. Specifically, we aimed to elucidate the neurobiology of underlying stress and metabolic dysfunction with a focus on sex-specific differences. We recognize that stress and metabolic disorders often co-occur and exhibit distinct patterns between sexes. In the present study, we observed that male mice fed a high-fat diet exhibited an inability to extinguish fear memory, mirroring a hallmark symptom observed in PTSD patients. We also observed sex-specific differences in metabolic and immune function in response to the diet and stress challenge. We uncovered that both repeated stress and a HFD can induce alterations in the quantity and types of immune cells present in various peripheral tissues, suggesting potential pathways through which metabolic diseases may develop. Our investigation further revealed that the ventromedial hypothalamus, responsible for regulating metabolism and stress behavior, exhibited distinct transcriptomic activity patterns in males and females. These findings shed light on the complex connections between high fat diet, stress levels, and overall health, emphasizing the importance of continued research in this area.


Assuntos
Dieta Hiperlipídica , Metabolismo Energético , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Estresse Psicológico , Animais , Masculino , Feminino , Estresse Psicológico/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo , Obesidade/metabolismo , Obesidade/psicologia , Comportamento Animal , Medo , Camundongos
3.
Function (Oxf) ; 5(4)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38984977

RESUMO

Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored. Here, we hypothesized that CETP impacts the perivascular adipose tissue (PVAT) phenotype and function in a sex-specific manner. PVAT function, gene and protein expression, and morphology were examined in male and female transgenic mice expressing human or simian CETP and their non-transgenic counterparts (NTg). PVAT exerted its anticontractile effect in aortas from NTg males, NTg females, and CETP females, but not in CETP males. CETP male PVAT had reduced NO levels, decreased eNOS and phospho-eNOS levels, oxidative stress, increased NOX1 and 2, and decreased SOD2 and 3 expressions. In contrast, CETP-expressing female PVAT displayed increased NO and phospho-eNOS levels with unchanged NOX expression. NOX inhibition and the antioxidant tempol restored PVAT anticontractile function in CETP males. Ex vivo estrogen treatment also restored PVAT function in CETP males. Moreover, CETP males, but not female PVAT, show increased inflammatory markers. PVAT lipid content increased in CETP males but decreased in CETP females, while PVAT cholesterol content increased in CETP females. CETP male PVAT exhibited elevated leptin and reduced Prdm16 (brown adipocyte marker) expression. These findings highlight CETP sex-specific impact on PVAT. In males, CETP impaired PVAT anticontractile function, accompanied by oxidative stress, inflammation, and whitening. Conversely, in females, CETP expression increased NO levels, induced an anti-inflammatory phenotype, and preserved the anticontractile function. This study reveals sex-specific vascular dysfunction mediated by CETP.


Assuntos
Tecido Adiposo , Proteínas de Transferência de Ésteres de Colesterol , Camundongos Transgênicos , Estresse Oxidativo , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Animais , Masculino , Feminino , Camundongos , Tecido Adiposo/metabolismo , Humanos , Caracteres Sexuais , Óxido Nítrico/metabolismo
4.
Sci Rep ; 14(1): 16020, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992236

RESUMO

Patients with degenerative cervical myelopathy (DCM) experience structural and functional brain reorganization. However, few studies have investigated the influence of sex on cerebral alterations. The present study investigates the role of sex on brain functional connectivity (FC) and global network topology in DCM and healthy controls (HCs). The resting-state functional MRI data was acquired for 100 patients (58 males vs. 42 females). ROI-to-ROI FC and network topological features were characterized for each patient and HC. Group differences in FC and network topological features were examined. Compared to healthy counterparts, DCM males exhibited higher FC between vision-related brain regions, and cerebellum, brainstem, and thalamus, but lower FC between the intracalcarine cortex and frontal and somatosensory cortices, while DCM females demonstrated higher FC between the thalamus and cerebellar and sensorimotor regions, but lower FC between sensorimotor and visual regions. DCM males displayed higher FC within the cerebellum and between the posterior cingulate cortex (PCC) and vision-related regions, while DCM females displayed higher FC between frontal regions and the PCC, cerebellum, and visual regions. Additionally, DCM males displayed significantly greater intra-network connectivity and efficiency compared to healthy counterparts. Results from the present study imply sex-specific supraspinal functional alterations occur in patients with DCM.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Doenças da Medula Espinal/fisiopatologia , Doenças da Medula Espinal/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Idoso , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Adulto , Caracteres Sexuais , Mapeamento Encefálico/métodos , Vias Neurais/fisiopatologia , Fatores Sexuais , Estudos de Casos e Controles
5.
Physiol Rep ; 12(13): e16110, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38981849

RESUMO

Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.


Assuntos
Animais Recém-Nascidos , Caracteres Sexuais , Transcriptoma , Masculino , Feminino , Animais , Ratos , Síndromes da Apneia do Sono/genética , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/fisiopatologia , Ratos Sprague-Dawley , Hipóxia/metabolismo , Hipóxia/genética , Hipóxia/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores Sexuais , Coração/fisiopatologia
6.
Nat Commun ; 15(1): 5752, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982135

RESUMO

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.


Assuntos
Proteoma , Proteômica , Animais , Proteoma/metabolismo , Camundongos , Feminino , Masculino , Proteômica/métodos , Rim/metabolismo , Rim/crescimento & desenvolvimento , Spliceossomos/metabolismo , Especificidade de Órgãos , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Fígado/metabolismo , Pulmão/metabolismo , Pulmão/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Caracteres Sexuais , Baço/metabolismo , Baço/crescimento & desenvolvimento
7.
Elife ; 122024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976495

RESUMO

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated waith AMP-activated protein kinase, peroxisome proliferator-activated receptor alpha, mammalian target of rapamycin, and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to food restriction.


Assuntos
Metabolismo Energético , Neocórtex , Animais , Feminino , Masculino , Neocórtex/fisiologia , Neocórtex/metabolismo , Camundongos , Córtex Visual/fisiologia , Córtex Visual/metabolismo , Fatores Sexuais , Privação de Alimentos/fisiologia , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Leptina/metabolismo , Leptina/sangue , Adaptação Fisiológica , Restrição Calórica
8.
Sci Adv ; 10(28): eadq3079, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996016

RESUMO

Sex and gender differences exist in the prevalence and clinical manifestation of common brain disorders. Identifying their neural correlates may help improve clinical care.


Assuntos
Encéfalo , Rede Nervosa , Caracteres Sexuais , Humanos , Encéfalo/fisiologia , Masculino , Feminino , Rede Nervosa/fisiologia , Fatores Sexuais , Mapeamento Encefálico
9.
Sci Adv ; 10(28): eadg1421, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996019

RESUMO

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (Ube3a) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that Ube3a overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.


Assuntos
Transtorno Autístico , Transcriptoma , Ubiquitina-Proteína Ligases , Animais , Masculino , Feminino , Transtorno Autístico/genética , Camundongos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Comportamento Animal , Caracteres Sexuais , Encéfalo/metabolismo , Modelos Animais de Doenças , Predisposição Genética para Doença
10.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000449

RESUMO

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue weight loss intervention and are more susceptible to the metabolic implications of obesity. In this narrative review, we comprehensively explored sex- and gender-specific differences in the development of obesity, focusing on a variety of biological variables, such as body composition, fat distribution and energy partitioning, the impact of sex steroid hormones and gut microbiota diversity, chromosomal and genetic variables, and behavioural and sociocultural variables influencing obesity development in men and women. Sex differences in obesity-related comorbidities and varying effectiveness of different weight loss interventions are also extensively discussed.


Assuntos
Obesidade , Caracteres Sexuais , Humanos , Obesidade/metabolismo , Feminino , Masculino , Microbioma Gastrointestinal , Hormônios Esteroides Gonadais/metabolismo , Fatores Sexuais , Composição Corporal , Redução de Peso
11.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39001095

RESUMO

Traffic accidents due to fatigue account for a large proportion of road fatalities. Based on simulated driving experiments with drivers recruited from college students, this paper investigates the use of heart rate variability (HRV) features to detect driver fatigue while considering sex differences. Sex-independent and sex-specific differences in HRV features between alert and fatigued states derived from 2 min electrocardiogram (ECG) signals were determined. Then, decision trees were used for driver fatigue detection using the HRV features of either all subjects or those of only males or females. Nineteen, eighteen, and thirteen HRV features were significantly different (Mann-Whitney U test, p < 0.01) between the two mental states for all subjects, males, and females, respectively. The fatigue detection models for all subjects, males, and females achieved classification accuracies of 86.3%, 94.8%, and 92.0%, respectively. In conclusion, sex differences in HRV features between drivers' mental states were found according to both the statistical analysis and classification results. By considering sex differences, precise HRV feature-based driver fatigue detection systems can be developed. Moreover, in contrast to conventional methods using HRV features from 5 min ECG signals, our method uses HRV features from 2 min ECG signals, thus enabling more rapid driver fatigue detection.


Assuntos
Condução de Veículo , Eletrocardiografia , Fadiga , Frequência Cardíaca , Humanos , Masculino , Frequência Cardíaca/fisiologia , Eletrocardiografia/métodos , Feminino , Fadiga/fisiopatologia , Fadiga/diagnóstico , Adulto Jovem , Adulto , Acidentes de Trânsito , Fatores Sexuais , Processamento de Sinais Assistido por Computador , Caracteres Sexuais
12.
Autoimmunity ; 57(1): 2377098, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39004847

RESUMO

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.


Assuntos
Modelos Animais de Doenças , Rim , Lúpus Eritematoso Sistêmico , Camundongos Endogâmicos MRL lpr , Animais , Feminino , Masculino , Camundongos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Rim/patologia , Rim/imunologia , Inflamação/imunologia , Inflamação/patologia , Fatores Sexuais , Baço/imunologia , Baço/patologia , Humanos , Caracteres Sexuais , Autoanticorpos/imunologia
13.
Neurobiol Aging ; 141: 151-159, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38954878

RESUMO

Decline in spatial context memory emerges in midlife, the time when most females transition from pre- to post-menopause. Recent evidence suggests that, among post-menopausal females, advanced age is associated with functional brain alterations and lower spatial context memory. However, it is unknown whether similar effects are evident for white matter (WM) and, moreover, whether such effects contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using a face-location memory paradigm, while WM microstructure was assessed using diffusion tensor imaging. Behaviorally, advanced age was associated with lower spatial context memory in post-menopausal females but not pre-menopausal females or males. Additionally, advanced age was associated with microstructural variability in predominantly frontal WM (e.g., anterior corona radiata, genu of corpus callosum), which was related to lower spatial context memory among post-menopausal females. Our findings suggest that post-menopausal status enhances vulnerability to age effects on the brain's WM and episodic memory.


Assuntos
Envelhecimento , Imagem de Tensor de Difusão , Menopausa , Caracteres Sexuais , Memória Espacial , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Feminino , Pessoa de Meia-Idade , Masculino , Memória Espacial/fisiologia , Envelhecimento/patologia , Envelhecimento/psicologia , Envelhecimento/fisiologia , Menopausa/fisiologia , Menopausa/psicologia , Adulto , Pós-Menopausa/fisiologia , Pós-Menopausa/psicologia , Memória Episódica
14.
Neurobiol Aging ; 141: 160-170, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38964013

RESUMO

Women have a higher incidence of Alzheimer's disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.


Assuntos
Doença de Alzheimer , Cognição , Disfunção Cognitiva , Peptidilprolil Isomerase de Interação com NIMA , Neocórtex , Emaranhados Neurofibrilares , Caracteres Sexuais , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Humanos , Feminino , Neocórtex/patologia , Neocórtex/metabolismo , Masculino , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Idoso , Idoso de 80 Anos ou mais , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/metabolismo , Fenótipo , Sistema Límbico/patologia , Sistema Límbico/metabolismo , Expressão Gênica , Envelhecimento/patologia , Envelhecimento/genética , Envelhecimento/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Fosforilação
15.
J Comp Neurol ; 532(7): e25658, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38987904

RESUMO

Spinal cord injury (SCI) disrupts coordination between the bladder and the external urinary sphincter (EUS), leading to transient or permanent voiding impairment, which is more severe in males. Male versus female differences in spinal circuits related to the EUS as well as post-SCI rewiring are essential for understanding of sex-/gender-specific impairments and possible recovery mechanisms. To quantitatively assess differences between EUS circuits in males versus females and in spinal intact (SI) versus SCI animals, we retrogradely traced and counted EUS-related neurons. In transgenic ChAT-GFP mice, motoneurons (MNs), interneurons (INs), and propriospinal neurons (PPNs) were retrogradely trans-synaptically traced with PRV614-red fluorescent protein (RFP) injected into EUS. EUS-MNs in dorsolateral nucleus (DLN) were separated from other GFP+ MNs by tracing them with FluoroGold (FG). We found two morphologically distinct cell types in DLN: FG+ spindle-shaped bipolar (SB-MNs) and FG- rounded multipolar (RM-MNs) cholinergic cells. Number of MNs of both types in males was twice as large as in females. SCI caused a partial loss of MNs in all spinal nuclei. After SCI, males showed a fourfold rise in the number of RFP-labeled cells in retro-DLN (RDLN) innervating hind limbs. This suggests (a) an existence of direct synaptic interactions between spinal nuclei and (b) a post-SCI increase of non-specific inputs to EUS-MNs from other motor nuclei. Number of INs and PPNs deferred between males and females: In SI males, the numbers of INs and PPNs were ∼10 times larger than in SI females. SCI caused a twofold decrease of INs and PPNs in males but not in females.


Assuntos
Camundongos Transgênicos , Caracteres Sexuais , Traumatismos da Medula Espinal , Uretra , Animais , Feminino , Masculino , Camundongos , Uretra/inervação , Uretra/fisiologia , Medula Espinal , Neurônios Motores/fisiologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Vias Neurais/fisiologia
17.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999932

RESUMO

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis (Mtb) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb-HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8+ cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold (p ≤ 0.01) and 1.7-fold (p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8+ cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ (p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8+ T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8+ cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8+ cell activation.


Assuntos
Tecido Adiposo , Pulmão , Mycobacterium tuberculosis , Animais , Feminino , Masculino , Camundongos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Pulmão/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/microbiologia , Camundongos Transgênicos , Fatores Sexuais , Modelos Animais de Doenças , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Caracteres Sexuais , Camundongos Endogâmicos C57BL
18.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999939

RESUMO

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein-metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.


Assuntos
Cardiomiopatia Dilatada , Humanos , Masculino , Feminino , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Pessoa de Meia-Idade , Caracteres Sexuais , Idoso , Função Ventricular Esquerda , Espectrometria de Massas em Tandem/métodos , Proteínas Sanguíneas/metabolismo , Adulto , Volume Sistólico , Biomarcadores/sangue , Fatores Sexuais , Metaboloma
19.
Neurosurg Focus ; 57(1): E9, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950448

RESUMO

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.


Assuntos
Atletas , Traumatismos em Atletas , Concussão Encefálica , Estudantes , Humanos , Masculino , Feminino , Concussão Encefálica/epidemiologia , Adolescente , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Recuperação de Função Fisiológica/fisiologia , Fatores Sexuais , Aprendizagem/fisiologia , Estudos de Coortes , Estudos Prospectivos , Instituições Acadêmicas , Retorno à Escola , Volta ao Esporte
20.
J Clin Invest ; 134(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949020

RESUMO

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.


Assuntos
Epigênese Genética , Neoplasias , Caracteres Sexuais , Humanos , Feminino , Neoplasias/genética , Masculino , Animais , Inativação do Cromossomo X , Hormônios Esteroides Gonadais/metabolismo , Impressão Genômica
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