Astrocyte Dysfunction Induced by Alcohol in Females but Not Males.
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ABSTRACT:
SUBMITTER: Wilhelm CJ
PROVIDER: S-EPMC8028916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Whether females should prefer to mate with old males is controversial. Old males may sire offspring of low quality because of an aging germline, but their proven ability to reach an old age can also be an excellent indicator of superior genetic quality, especially in natural populations. These genetic effects are, however, hard to study in nature, because they are often confounded with direct benefits offered by old males to the female, such as experience and high territory quality. We, therefore, used naturally occurring extra-pair young to disentangle different aspects of male age on female fitness in a natural population of collared flycatchers because any difference between within- and extra-pair young within a nest should be caused by paternal genetic effects only. Based on 18 years of long-term data, we found that females paired with older males as social partners experienced an overall reproductive advantage. However, offspring sired by old males were of lower quality as compared to their extra-pair half-siblings, whereas the opposite was found in nests attended by young males. These results imply a negative genetic effect of old paternal age, given that extra-pair males are competitive middle-age males. Thus, offspring may benefit from being sired by young males but raised by old males, to maximize both genetic and direct effects. Our results show that direct and genetic benefits from pairing with old males may act in opposing directions and that the quality of the germline may deteriorate before other signs of senescence become obvious.
| S-EPMC8484724 | biostudies-literature
Project description:BackgroundWe previously reported that ethanol-containing liquid diet feeding induces osteonecrosis of the femoral head in male rats. Also, it was reported that a large amount of consumed ethanol and a long-term history of drinking were risk factors for osteonecrosis of the femoral head, and that the frequency of alcohol-induced osteonecrosis of the femoral head in males was much greater than in females. The higher incidence of alcohol-induced osteonecrosis of the femoral head could be due to either higher prevalence of alcohol drinking in males or due to their potential higher sensitivity to alcohol. The aim of the study is to investigate the influence of alcohol consumption and drinking period on the development of osteonecrosis of the femoral head in rats of both sex.MethodsAll the experimental male rats were allocated to the male one-month ethanol drinking group (M1). Female rats were randomly divided into the female one- to five-months ethanol drinking groups (F1-5). All rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol for one to five months.ResultsOne-month feeding with the ethanol-containing liquid diet resulted in the development of osteonecrosis of the femoral head in seven of twenty in the M1 group, but none in the F1 group, although the mean intake of ethanol per body weight in the M1 group was significantly lower than that in the F1 group. Furthermore, long drinking periods with a large amount of ethanol intake in the F2-5 groups did not induce osteonecrosis of the femoral head.ConclusionThe present study shows that lower alcohol consumption over short periods of time that were sufficient to induce osteonecrosis of the femoral head in males had no effect on females. Even with greater alcohol consumption and longer duration, females did not develop osteonecrosis of the femoral head. Therefore, unknown factors related to sex must be responsible for the development of this condition.
| S-EPMC5082908 | biostudies-literature
Project description:BackgroundApproximately one quarter of persons exposed to hepatitis C virus (HCV) will spontaneously clear infection. We undertook this study to investigate the impact of alcohol on likelihood of HCV spontaneous viral clearance stratified by sex groups.MethodsPooled data from an international collaboration of prospective observational studies of incident HIV and HCV infection in high-risk cohorts (the InC3 Study) was restricted to 411 persons (or 560.7 person-years of observation) with documented acute HCV infection and data regarding alcohol use. The predictor of interest was self-reported alcohol use at or after estimated date of incident HCV infection and the outcome was HCV spontaneous clearance. Sex stratified Cox proportional hazards models were used to evaluate the association between alcohol and spontaneous clearance, adjusting for age, race/ethnicity, and IFNL4 genotype.ResultsThe median age was 28.5 years, 30.4% were women, 87.2% were white, and 71.8% reported alcohol use at or after incident infection. There were 89 (21.6%) cases of spontaneous clearance observed, 39 (31.2%) among women and 50 (17.5%) in men (p<0.01). Overall, spontaneous clearance occurred less frequently among participants who drank alcohol compared to those who did not drink (18.9% v. 28.5%, p=0.03). After adjustment for other covariates, alcohol was significantly and independently associated with lower relative hazards for spontaneous clearance of HCV in women (AHR=0.35; 95% CI: 0.19-0.66; p=0.001) but not in men (AHR=0.63; 95% CI: 0.36-1.09; p=0.10).ConclusionResults indicate that abstaining from drinking alcohol may increase the likelihood of spontaneous clearance among women.
| S-EPMC5328754 | biostudies-literature
Project description:ContextCold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest at the start of the wakeful period.ObjectiveWe investigated whether cold-induced thermogenesis displays diurnal variation in humans and differs between the sexes.MethodsThis randomized crossover study included 24 young and lean male (n = 12) and female (n = 12) participants who underwent 2.5-hour personalized cooling using water-perfused mattresses in the morning (7:45 am) and evening (7:45 pm), with 1 day in between. We measured energy expenditure (EE) and supraclavicular skin temperature in response to cold exposure.ResultsIn males, cold-induced EE was higher in the morning than in the evening (+54% ± 10% vs +30% ± 7%; P = 0.05) but did not differ between morning and evening in females (+37% ± 9% vs +30% ± 10%; P = 0.42). Only in males, supraclavicular skin temperature upon cold increased more in morning than evening (+0.2 ± 0.1 °C vs -0.2 ± 0.2 °C; P = 0.05). In males, circulating free fatty acid (FFA) levels were increased after morning cold exposure, but not evening (+90% ± 18% vs +9% ± 8%; P < 0.001). In females, circulating FFA (+94% ± 21% vs +20% ± 5%; P = 0.006), but also triglycerides (+42% ± 5% vs +29% ± 4%, P = 0.01) and cholesterol levels (+17% ± 2% vs 11% ± 2%; P = 0.05) were more increased after cold exposure in morning than in evening.ConclusionCold-induced thermogenesis is higher in morning than evening in males; however, lipid metabolism is more modulated in the morning than the evening in females.
| S-EPMC9113803 | biostudies-literature
Project description:Males and females are subject to differences in cognitive processing strategies, i.e. the way males and females solve cognitive tasks. So far primarily reported for younger adults, this seems to be especially important in older adults, who also show sex differences in cognitive impairments. Therefore, the aim of the current study was to examine the older adult population with respect to cognitive profiles derived from a large variety of cognitive functions. Using an exploratory component analysis with consecutive confirmatory factor analysis in a sample of 676 older adults, neuropsychological performance data in a variety of cognitive domains was decomposed into cognitive components. A general cognitive profile based on the whole group fits unequally well on the two sexes. Importantly, cognitive profiles based on either males or females differ in terms of their composition of cognitive components, i.e. three components in males versus four components in females, with a generally better model fit in females. Thus, related to the established differences in processing styles between males and females the current study found a rather decomposed (or local) cognitive profile in females while males seem to show a holistic (or global) cognitive profile, with more interrelations between different cognitive functions.
| S-EPMC7985508 | biostudies-literature
Project description:BackgroundAcidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury.ResultsExperiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons.ConclusionOur studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously.
| S-EPMC4608795 | biostudies-literature
Project description:Women are more sensitive to the harmful effects of alcohol (EtOH) abuse than men, yet the underlying mechanisms remain poorly understood. Previous gene expression analysis of the medial prefrontal cortex (mPFC) following a chronic intoxication paradigm using continuous 72 h vapor inhalation found that females, but not males, exhibit an inflammatory response at peak withdrawal that is associated with cell damage. Given that glucocorticoids can function as anti-inflammatories, are known to increase with EtOH exposure, and influence neurotoxicity, we hypothesized that males and females may exhibit an altered corticosterone (CORT) response following chronic intoxication. Analysis of serum CORT levels revealed the expected increase during withdrawal with no difference between males and females, while control males but not females exhibited higher CORT concentrations than naive animals. Glucocorticoid signaling characterized using focused qPCR arrays identified a sexually dimorphic response in the mPFC during withdrawal, particularly among astrocyte-enriched genes. These genes include aquaporin-1 (Aqp1), sphingosine kinase 1 (Sphk1) and connective tissue growth factor (Ctgf); genes associated with inflammatory signaling, and tissue damage and repair. Bioinformatic analysis also revealed activation of inflammatory signaling and cell death pathways in females. Confirmation studies showed that female mice exhibited significant neuronal degeneration within the anterior cingulate cortex (ACC). By contrast, EtOH exposure lead to a significant reduction in cell death in males. Thus, distinct glucocorticoid signaling pathways are associated with sexually dimorphic neurotoxicity, suggesting one mechanism by which EtOH-exposed females are particularly vulnerable to the damaging effects of alcohol in the CNS.
| S-EPMC4362524 | biostudies-literature
Project description:Previously we have shown that chronic alcohol intake causes alcohol-induced ciliary dysfunction (AICD), leading to non-responsive airway cilia. AICD likely occurs through the downregulation of nitric oxide (NO) and cyclic nucleotide-dependent kinases, protein kinase G (PKG) and protein kinase A (PKA). Studies by others have shown that dietary supplementation with the antioxidants N-acetylcysteine (NAC) and procysteine prevent other alcohol-induced lung complications. This led us to hypothesize that dietary supplementation with NAC or procysteine prevents AICD. To test this hypothesis, C57BL/6 mice drank an alcohol/water solution (20% w/v) ad libitum for 6 weeks and were concurrently fed dietary supplements of either NAC or procysteine. Ciliary beat frequency (CBF) was measured in mice tracheas, and PKG/PKA responsiveness to ?-agonists and NOx levels were measured from bronchoalveolar lavage (BAL) fluid. Long-term alcohol drinking reduced CBF, PKG and PKA responsiveness to ?-agonists, and lung NOx levels in BAL fluid. In contrast, alcohol-drinking mice fed NAC or procysteine sustained ciliary function and PKG and PKA responsiveness to ?-agonists. However, BAL NO levels remained low despite antioxidant supplementation. We also determined that removal of alcohol from the drinking water for as little as 1 week restored ciliary function, but not PKG and PKA responsiveness to ?-agonists. We conclude that dietary supplementation with NAC or procysteine protects against AICD. In addition, alcohol removal for 1 week restores cilia function independent of PKG and PKA activity. Our findings provide a rationale for the use of antioxidants to prevent damage to airway mucociliary functions in chronic alcohol-drinking individuals.
| S-EPMC3850762 | biostudies-literature
Project description:Adolescence is a developmental period characterized by significant changes in brain architecture and behaviour. The immaturity of the adolescent brain is associated with heightened vulnerability to exogenous agents, including alcohol. Alcohol is the most consumed drug among teenagers, and binge-drinking during adolescence is a major public health concern. Studies have suggested that adolescent alcohol exposure may interfere with the maturation of frontal brain regions and lead to long-lasting behavioural consequences. In this study, by using a slightly modified version of the Drinking in the Dark paradigm, adolescent C57Bl6 mice reach high blood alcohol concentration after voluntary binge-drinking. In order to assess short- and long-term consequences of adolescent alcohol exposure (AAE), a battery of behavioural tests was performed during late adolescence and during adulthood. We showed that AAE had no short-term effect on young mice behaviour but rather increased anxiety- and depressive-like behaviours, as well as alcohol consumption during adulthood. Moreover, alcohol binge-drinking during adolescence dramatically decreased recognition memory performances and behavioural flexibility in both adult males and females. Furthermore, we showed that voluntary consumption of alcohol during adolescence did not trigger any major activation of the innate immune system in the prefrontal cortex. Together, our data suggest that voluntary alcohol binge-drinking in adolescent mice induces a delayed appearance of behavioural impairments in adulthood.
| S-EPMC9285796 | biostudies-literature
Project description:The clinical difference between nonalcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) between the two sexes is unclear. This study aimed to determine the influences of alcohol consumption and qualitative abdominal fat between male and female patients with NAFLD and MAFLD. This cross-sectional study examined 11,766 participants who underwent health check-ups comparing lifestyle habits, biochemical features, and noninvasive liver fibrosis scores, between non-MAFLD and MAFLD groups. Furthermore, differences in alcohol consumption and qualitative abdominal fat were examined between male and female patients with NAFLD and MAFLD. The prevalence of metabolic dysregulation, ratio of visceral fat area to subcutaneous fat area, and noninvasive liver fibrosis scores were significantly higher in male patients with MAFLD than in those with NAFLD (p < 0.05), but these were not significantly different in female patients. Among male patients with an alcohol consumption of > 70 g/week, several noninvasive liver fibrosis scores were significantly higher in the MAFLD group than in the NAFLD group (all p < 0.05). The influences of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD were different between sexes. The development of liver fibrosis should be considered in male patients with MAFLD who exceed mild drinking.
| S-EPMC9512786 | biostudies-literature