scholarly journals Sex differences in Variability of Brain Structure Across the Lifespan

2019 ◽  
Author(s):  
Natalie J Forde ◽  
Jerrold Jeyachandra ◽  
Michael Joseph ◽  
Grace R Jacobs ◽  
Erin Dickie ◽  
...  
Keyword(s):  
Sex Differences ◽  
Early Life ◽  
Disease Risk ◽  
Late Life ◽  
Brain Regions ◽  
Variance Ratio ◽  
Regional Variability ◽  
Protective Mechanisms ◽  
Structural Covariance ◽  
Subcortical Volumes

AbstractSeveral brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences across the lifespan can provide insight into potential disease risk and protective mechanisms. We focused on sex-related differences in variability, which may be indicative of both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females vs. males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. Multivariate analysis that accounts for structural covariance supported variance ratio findings. Findings were present from early life and stable with age. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.

scholarly journals Sex Differences in Variability of Brain Structure Across the Lifespan

2020 ◽  
Vol 30 (10) ◽  
pp. 5420-5430
Author(s):  
Natalie J Forde ◽  
Jerrold Jeyachandra ◽  
Michael Joseph ◽  
Grace R Jacobs ◽  
Erin Dickie ◽  
...  
Keyword(s):  
Sex Differences ◽  
Early Life ◽  
Late Life ◽  
Brain Regions ◽  
Brain Disorders ◽  
Regional Variability ◽  
Structural Covariance ◽  
Males And Females ◽  
Insight Into ◽  
Subcortical Volumes

Abstract Several brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences in variability across the lifespan can provide insight into both disease vulnerability and resilience. In n = 3069 participants, from 8 to 95 years of age, we found widespread greater variability in males compared with females in cortical surface area and global and subcortical volumes for discrete brain regions. In contrast, variance in cortical thickness was similar for males and females. These findings were supported by multivariate analysis accounting for structural covariance, and present and stable across the lifespan. Additionally, we examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared with females, while in very late life this was reversed. Overall, our findings of greater regional variability, but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.

scholarly journals Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood

2020 ◽  
Vol 117 (38) ◽  
pp. 23751-23761 ◽  
Author(s):  
Emily Mackey ◽  
Kyan M. Thelen ◽  
Vedrana Bali ◽  
Mahsa Fardisi ◽  
Madalyn Trowbridge ◽  
...  
Keyword(s):  
Sex Differences ◽  
Early Life ◽  
Disease Risk ◽  
Sex Bias ◽  
Factors Affecting ◽  
Associated Diseases ◽  
Androgen Exposure ◽  
Host Sex ◽  
Increase Risk ◽  
High Level

Mast cell (MC)-associated diseases, including allergy/anaphylaxis and neuroinflammatory pain disorders, exhibit a sex bias, with females at increase risk. While much attention has been directed toward adult sex hormones as drivers of sex differences, that female sex bias in MC-associated diseases is evident in prepubertal children, suggesting early-life origins of sex differences which have yet to be explored. Utilizing rodent models of MC-mediated anaphylaxis, our data here reveal that, 1) compared with females, males exhibit significantly reduced severity of MC-mediated anaphylactic responses that emerge prior to puberty and persist into adulthood, 2) reduced severity of MC-mediated anaphylaxis in males is linked with the naturally high level of perinatal androgens and can be recapitulated in females by perinatal exposure to testosterone proprionate, 3) perinatal androgen exposure guides bone marrow MC progenitors toward a masculinized tissue MC phenotype characterized by decreased concentration of prestored MC granule mediators (e.g., histamine, serotonin, and proteases) and reduced mediator release upon degranulation, and 4) engraftment of MC-deficient KitW-sh/W-shmice with adult male, female, or perinatally androgenized female MCs results in MC-mediated anaphylaxis response that reflects the MC sex and not host sex. Together, these data present evidence that sex differences in MC phenotype and resulting disease severity are established in early life by perinatal androgens. Thus, factors affecting levels of perinatal androgens could have a significant impact on MC development and MC-associated disease risk across the life span.

scholarly journals Modulation of the Hypothalamic Nutrient Sensing Pathways by Sex and Early-Life Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Silvie R. Ruigrok ◽  
Nina Stöberl ◽  
Kit-Yi Yam ◽  
Chiara de Lucia ◽  
Paul J. Lucassen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Life Stress ◽  
Early Life ◽  
Disease Risk ◽  
Energy State ◽  
Early Life Stress ◽  
Nutrient Sensing ◽  
Future Research ◽  
Expression Of Genes

There are sex differences in metabolic disease risk, and early-life stress (ES) increases the risk to develop such diseases, potentially in a sex-specific manner. It remains to be understood, however, how sex and ES affect such metabolic vulnerability. The hypothalamus regulates food intake and energy expenditure by sensing the organism’s energy state via metabolic hormones (leptin, insulin, ghrelin) and nutrients (glucose, fatty acids). Here, we investigated if and how sex and ES alter hypothalamic nutrient sensing short and long-term. ES was induced in mice by limiting the bedding and nesting material from postnatal day (P)2-P9, and the expression of genes critical for hypothalamic nutrient sensing were studied in male and female offspring, both at P9 and in adulthood (P180). At P9, we observed a sex difference in both Ppargc1a and Lepr expression, while the latter was also increased in ES-exposed animals relative to controls. In adulthood, we found sex differences in Acacb, Agrp, and Npy expression, whereas ES did not affect the expression of genes involved in hypothalamic nutrient sensing. Thus, we observe a pervasive sex difference in nutrient sensing pathways and a targeted modulation of this pathway by ES early in life. Future research is needed to address if the modulation of these pathways by sex and ES is involved in the differential vulnerability to metabolic diseases.

scholarly journals Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saira Khan ◽  
K. Y. Wolin ◽  
R. Pakpahan ◽  
R. L. Grubb ◽  
G. A. Colditz ◽  
...  
Keyword(s):  
Body Size ◽  
Benign Prostatic Hyperplasia ◽  
Life Course ◽  
Early Life ◽  
Prostate Volume ◽  
Late Life ◽  
Later Life ◽  
Normal Weight ◽  
Prostatic Hyperplasia ◽  
The Life Course

Abstract Background Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. Methods Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. Results Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11–1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07–1.21; RRobese: 1.10, 95% CI 1.02–1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98–1.22; RRnormal to obese: 1.28, 95% CI 1.10–1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05–1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. Conclusions We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

P.207 Sex differences in cocaine consumption vulnerability induced by early-life stress in mice

2021 ◽  
Vol 44 ◽  
pp. S20-S21
Author(s):  
A. Castro-Zavala ◽  
A. Martín-Sánchez ◽  
L. Montalvo-Martínez ◽  
A. Camacho-Morales ◽  
O. Valverde
Keyword(s):  
Sex Differences ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

scholarly journals Vascular disease/risk and late-life depression in a Korean community population

2004 ◽  
Vol 185 (2) ◽  
pp. 102-107 ◽  
Author(s):  
Jae-Min Kim ◽  
Robert Stewart ◽  
Il-Seon Shin ◽  
Jin-Sang Yoon
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Vascular Disease ◽  
Disease Risk ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Late Life ◽  
Late Life Depression ◽  
Previous Stroke ◽  
Community Population

BackgroundAssociations between vascular risk factors and late-life depression are controversial.AimsTo investigate the association between measures of vascular disease/ risk and depression and confounding and effect modification by APOE genotype and cognitive function.MethodIn a Korean community population aged 65+ (n=732), diagnosis of depression (Geriatric Mental State Schedule) and information on vascular status, disability, APOE genotype and cognitive function were obtained.ResultsPrevious stroke and lower high-density lipoprotein cholesterol level (but neither hypertension nor diabetes) were significantly associated with depression (independently of disability and cognitive function). These associations were stronger in participants with borderline cognitive impairment, although not to a significant extent.ConclusionsExcept for previous stroke and an atherogenic lipid profile, associations between depression and other common risk factors for cerebrovascular disease were not evident.

Sex differences in brain regions activated by grammatical and reading tasks

Neuroreport ◽  
1998 ◽  
Vol 9 (12) ◽  
pp. 2803-2807 ◽  
Author(s):  
Jeri J. Jaeger ◽  
Alan H. Lockwood ◽  
Robert D. Van Valin ◽  
David L. Kemmerer ◽  
Brian W. Murphy ◽  
...  
Keyword(s):  
Sex Differences ◽  
Brain Regions

scholarly journals A pH-eQTL interaction at the RIT2-SYT4 Parkinson's disease risk locus in the substantia nigra

2020 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Leon French
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Human Brain ◽  
Disease Risk ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Postmortem Human Brain ◽  
Increased Risk

BACKGROUND: Parkinson's disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson's disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. OBJECTIVE: To assess pH associations at the RIT2-SYT4 locus. METHODS: Linear models to examine two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. RESULTS: Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain. Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. CONCLUSIONS: These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.

scholarly journals Size at birth, lifecourse factors, and cognitive function in late life: findings from the MYsore study of Natal effects on Ageing and Health (MYNAH) cohort in South India

2021 ◽  
pp. 1-14
Author(s):  
Murali Krishna ◽  
Ghattu V. Krishnaveni ◽  
Veena Sargur ◽  
Kalyanaraman Kumaran ◽  
Mohan Kumar ◽  
...  
Keyword(s):  
Birth Weight ◽  
Cognitive Function ◽  
Brain Development ◽  
Educational Level ◽  
Early Life ◽  
South India ◽  
Late Life ◽  
Positive Effects ◽  
Cardiometabolic Disorders ◽  
Size At Birth

ABSTRACT Objective: To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming. Design: Longitudinal follow-up of a birth cohort. Setting: CSI Holdsworth Memorial Hospital (HMH), Mysore South India. Participants: 721 men and women (55–80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life. Measurements: Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders Results: Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants’ own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors and was attenuated after adjustment for all lifecourse factors (0.08 SD per SD birth weight [95% CI −0.01, 0.18] p = 0.07). Conclusions: The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.

scholarly journals Lifelong Cytomegalovirus and Early-Life Irradiation Synergistically Potentiate Age-Related Defects in Response to Vaccination and Infection

2021 ◽  
Author(s):  
Jason L. Pugh ◽  
Christopher P. Coplen ◽  
Alona S. Sukhina ◽  
Jennifer L. Uhrlaub ◽  
Jose Padilla-Torres ◽  
...  
Keyword(s):  
Dna Damage ◽  
Early Life ◽  
Acute Infection ◽  
Late Life ◽  
Whole Body ◽  
Murine Cytomegalovirus ◽  
Live Attenuated Vaccine ◽  
Age Related ◽  
Theory Of Aging ◽  
High Level

ABSTRACTA popular “DNA-damage theory” of aging posits that unrepaired DNA damage leads to cellular (and organismal) senescence. Indeed, some hallmarks of immune aging are more prevalent in individuals exposed to Whole-Body Irradiation (WBI). To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent Murine Cytomegalovirus (MCMV) and early-life WBI (i) over the course of the lifespan; (ii) in response to a West Nile virus (WNV) live attenuated vaccine; and (iii) following lethal WNV challenge subsequent to vaccination. We recently published that a single dose of non-lethal WBI in youth, on its own, was not sufficient to accelerate aging of the murine immune system despite causing widespread DNA damage and repopulation stress in hematopoietic cells. However, 4Gy sub-lethal WBI caused manifest reactivation of MCMV. Following vaccination and challenge with WNV in the old age, MCMV-infected animals experiencing 4Gy, but not lower, dose of sub-lethal WBI in youth had reduced survival. By contrast, old irradiated mice lacking MCMV and MCMV-infected, but not irradiated, mice were both protected to the same high level as the old non-irradiated, uninfected controls. Analysis of the quality and quantity of anti-WNV immunity showed that higher mortality in MCMV-positive WBI mice correlated with increased levels of MCMV-specific immune activation during WNV challenge. Moreover, we demonstrate that infection, including that by WNV, led to MCMV reactivation. Our data suggest that MCMV reactivation may be an important determinant of increased late-life mortality following early-life irradiation and late-life acute infection.

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