Male Impairment Research Articles

Dietary fat quality impacts metabolic impairments of type 2 diabetes risk differently in male and female CD-1® mice.

Metabolic impairments associated with type 2 diabetes, including insulin resistance and loss of glycaemic control, disproportionately impact the elderly. Lifestyle interventions, such as manipulation of dietary fat quality (i.e. fatty acid (FA) composition), have been shown to favourably modulate metabolic health. Yet, whether or not chronic consumption of beneficial FAs can protect against metabolic derangements and disease risk during ageing is not well defined. We sought to evaluate whether long-term dietary supplementation of fish-, dairy- or echium-derived FAs to the average FA profile in a U.S. American diet may offset metabolic impairments in males and females during ageing. One-month-old CD-1® mice were fed isoenergetic, high-fat (40 %) diets with the fat content composed of either 100 % control fat blend (CO) or 70 % CO with 30 % fish oil, dairy fat or echium oil for 13 months. Every 3 months, parameters of glucose homoeostasis were evaluated via glucose and insulin tolerance tests. Glucose tolerance improved in males consuming a diet supplemented with fish oil or echium oil as ageing progressed, but not in females. Yet, females were more metabolically protected than males regardless of age. Additionally, Spearman correlations were performed between indices of glucose homoeostasis and previously reported measurements of diet-derived FA content in tissues and colonic bacterial composition, which also revealed sex-specific associations. This study provides evidence that long-term dietary fat quality influences risk factors of metabolic diseases during ageing in a sex-dependent manner; thus, sex is a critical factor to be considered in future dietary strategies to mitigate type 2 diabetes risk.

Sex difference in the association between solid fuel use and cognitive function in rural China

BackgroundWhether indoor air pollution from solid fuel use is associated with cognitive function remains unclear. ObjectiveThis study aims to examine the association of solid fuel use with the risk of cognitive impairment in males and females. MethodsThe data was from the China Health and Retirement Longitudinal Study (CHARLS). Self-reported heating and cooking fuel were categorized as clean fuel (solar, liquefied gas, natural gas, or electricity) and solid fuel (coal, biomass charcoal, wood, or straw). Cognitive function, including orientation and attention, episodic memory, and visuospatial abilities, was assessed using standardized questionnaires. ResultsA total of 7824 individuals were included in our study (aged 57.0 ± 9.3, 46.2% female), with 47.0% and 76.0% used solid fuel for cooking and heating, respectively. There was an interaction between sex and solid fuel use for cooking (P=0.008) for the progress of cognitive impairment. Solid fuel use for cooking was associated with a larger decrease in cognitive function score in females (β=−0.832; 95% CI: −1.043, −0.622; P < 0.001) than in males (β=−0.487; 95% CI: −0.671, −0.302; P < 0.001). The sex difference remained with further adjustment of covariates (β=−0.321; 95% CI: −0.503, −0.138; P=0.001 for males; β=−0.534; 95% CI: −0.745, −0.324; P < 0.001 for females). For heating, the interaction between sex and solid fuel was not statistically significant (P=0.156). After controlling for the covariates, solid fuel use for heating was inversely associated with a 0.321 unit of decrease of cognitive function score (β=−0.321; 95% CI: −0.652, 0.009; P=0.057) in males, and a 0.598 unit of decrease of cognitive function (β=−0.598; 95% CI: −0.978, −0.218; P=0.002) in females. ConclusionIn conclusion, solid fuel use for cooking and heating was significantly associated with a higher risk of cognitive impairment. Furthermore, for the first time, we found that the effect of solid fuel use on cognitive function in females was greater than in males.

Effects of running before pregnancy on long-term memory and hippocampal alterations induced by prenatal stress

Studies have shown that an adverse environment in utero influences fetal growth and development, leading to several neuroendocrine and behavioral changes in adult life. Nevertheless, the mechanisms involved in the long-term benefits of pregestational exercise are still poorly understood. Thus, this study aimed to evaluate the effects of physical exercise before the gestational period on memory behavior and gene expression in the hippocampus of adult mice submitted to prenatal stress. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). When adults, male and female offspring were submitted to the object recognition test followed by the hippocampal evaluation of BDNF exons I and IV mRNA expression, as well as hypothalamic-pituitary-adrenal axis related genes. Pregestational exercise did not prevent the decreased recognition index, as well as GR and CRHR1 gene expression observed in PNS males. Conversely, prenatal stress did not influence female memory behavior. Moreover, exercise attenuated the effects of prenatal stress on female BDNF IV gene expression. The results indicate that pregestational exercise was able to prevent the effects of maternal stress on hippocampal BDNF IV gene expression in females, although no effects were seen on the stress-induced memory impairment in males.

Unexpected Role of Physiological Estrogen in Acute Stress-Induced Memory Deficits.

Stress may promote emotional and cognitive disturbances, which differ by sex. Adverse outcomes, including memory disturbances, are typically observed following chronic stress, but are now being recognized also after short events, including mass shootings, assault, or natural disasters, events that consist of concurrent multiple acute stresses (MAS). Prior work has established profound and enduring effects of MAS on memory in males. Here we examined the effects of MAS on female mice and probed the role of hormonal fluctuations during the estrous cycle on MAS-induced memory problems and the underlying brain network and cellular mechanisms. Female mice were impacted by MAS in an estrous cycle-dependent manner: MAS impaired hippocampus-dependent spatial memory in early-proestrous mice, characterized by high levels of estradiol, whereas memory of mice stressed during estrus (low estradiol) was spared. As spatial memory requires an intact dorsal hippocampal CA1, we examined synaptic integrity in mice stressed at different cycle phases and found a congruence of dendritic spine density and spatial memory deficits, with reduced spine density only in mice stressed during high estradiol cycle phases. Assessing MAS-induced activation of brain networks interconnected with hippocampus, we identified differential estrous cycle-dependent activation of memory- and stress-related regions, including the amygdala. Network analyses of the cross-correlation of fos expression among these regions uncovered functional connectivity that differentiated impaired mice from those not impaired by MAS. In conclusion, the estrous cycle modulates the impact of MAS on spatial memory, and fluctuating physiological levels of sex hormones may contribute to this effect.SIGNIFICANCE STATEMENT: Effects of stress on brain functions, including memory, are profound and sex-dependent. Acute stressors occurring simultaneously result in spatial memory impairments in males, but effects on females are unknown. Here we identified estrous cycle-dependent effects of such stresses on memory in females. Surprisingly, females with higher physiological estradiol experienced stress-induced memory impairment and a loss of underlying synapses. Memory- and stress-responsive brain regions interconnected with hippocampus were differentially activated across high and low estradiol mice, and predicted memory impairment. Thus, at functional, network, and cellular levels, physiological estradiol influences the effects of stress on memory in females, providing insight into mechanisms of prominent sex differences in stress-related memory disorders, such as post-traumatic stress disorder.

Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters

Degeneration of substantia nigra pars compacta dopamine neurons is a central feature in the pathology of Parkinson’s disease, which is characterized by progressive loss of motor and cognitive functions. The largest risk factors for Parkinson’s disease are age and sex; most cases occur after age 60 and males have nearly twice the incidence as females. Preclinical work has scarcely considered the influence of these 2 factors to disease risk and presentation. Here, we observed a progressive decline in dopamine neuron firing activity in male C57BL/6 mice by 18 months of age, while dopamine neurons from females remained largely unaffected. This was accompanied by increased mRNA expression of PINK1 in both males and females, and PARK2 primarily in males, both of which have been linked to Parkinson’s. Since the declining cell properties were accompanied by only slight decreases in locomotion in both sexes, it is likely that these age-related impairments in males represent a vulnerability to further insults that could predispose the neurons to neurodegenerative processes such as in Parkinson’s.

4333 The role of the L-type calcium channel, Cav1.3, in motor and associative learning

OBJECTIVES/GOALS: Genetic variation in L-type voltage-gated calcium channels, including CaV1.3, is associated with increased risk for psychiatric disorders including bipolar disorder and schizophrenia. Additionally, rare mutations in CaV1.3 have been linked to epilepsy, developmental delay, and autism. Deletion of CaV1.3 in mice is associated with impaired consolidation of contextual fear conditioning. Some studies have also observed affective behavior deficits in CaV1.3-deficient mice, but other studies have not found affective phenotypes, perhaps due to differences in genetic backgrounds, sex ratios, or task protocols. CaV1.3 is important for slow afterhyperpolarization in hippocampal and amygdala neurons, which prevents excessive firing in response to sustained excitatory input, and CaV1.3-deficient amygdala neurons exhibit hyperexcitability and impaired LTP. CaV1.3 is also expressed in the cerebellum, but its functional role there is not well understood. Given its importance in shaping neuronal activity in the hippocampus and amygdala, we hypothesized that loss of CaV1.3 would cause abnormalities in motor learning as well as affective and cognitive behaviors. METHODS/STUDY POPULATION: Wild-type (WT), haploinsufficient (Hap), and knockout (KO) mice were maintained on a congenic C57BL/6NTac genetic background and were subjected to behavioral tasks including open field, rotarod, ErasmusLadder, elevated zero maze, forced swim test, and tail suspension test. Data were analyzed with sexes combined and with sexes separated to assess for sex as a biological variable. Studies were analyzed by one-way ANOVA, two-way ANOVA, or generalized linear mixed model, where appropriate. RESULTS/ANTICIPATED RESULTS: CaV1.3 KO was associated with impaired motor learning in the rotarod task (p &lt; 0.05), as well as impaired associative learning in the ErasmusLadder task (p &lt; 0.01), despite intact locomotor function on both tasks. When examined by sex, the rotarod phenotypes were driven by motor learning impairments in males (both Hap and KO, p &lt; 0.05 and p &lt; 0.01, respectively), whereas the ErasmusLadder associative learning phenotypes were present in both sexes only in the KO condition, consistent with previously reported impairments in CaV1.3-deficient mice in consolidation of contextual fear conditioning. Although KO mice learned the motor aspects of the ErasmusLadder task, they learned more slowly. They also failed to learn start cues, which requires intact associative learning. No differences were observed in overall exploration or locomotor activity in open field or elevated zero maze. Analyses from affective tasks are ongoing. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary studies provide new evidence that CaV1.3 is important for the function of neural circuits involved in motor learning, and concur with previous data showing its involvement in associative learning. Our data differ slightly from previous studies of CaV1.3 in motor learning, which could be attributable to differences in task protocols and/or genetic background. These results highlight the importance of CaV1.3 in a variety of behaviors, which may help explain why variation in CaV1.3 expression and function has pleiotropic effects in humans.

Sex Differences in Cognitive Impairment Induced by Cerebral Microhemorrhage.

It has been suggested that cerebral microhemorrhages (CMHs) could be involved in cognitive decline. However, little is known about the sex-dependency of this effect. Using a multimodal approach combining behavioral tests, in vivo imaging, biochemistry, and molecular biology, we studied the cortical and hippocampal impact of a CMH in male and female mice (C57BL/6J) 6weeks post-induction using a collagenase-induced model. Our work shows for the first time that a single cortical CMH exerts sex-specific effects on cognition. It notably induced visuospatial memory impairment in males only. This sex difference might be explained by cortical changes secondary to the lesion. In fact, the CMH induced an upregulation of ERα mRNA only in the female cortex. Besides, in male mice, we observed an impairment of pathways associated to neuronal, glial, or vascular functions: decrease in the P-GSK3β/GSK3β ratio, in BDNF and VEGF levels, and in microvascular water mobility. The CMH also exerted spatial remote effects in the hippocampus by increasing the number of astrocytes in both sexes, increasing the mean area occupied by each astrocyte in males, and decreasing hippocampal BDNF in females suggesting a cortical-hippocampal network impairment. This work demonstrates that a CMH could directly affect cognition in a sex-specific manner and highlights the need to study both sexes in preclinical models.

Stimulation of Angiotensin II Receptor 2 Preserves Cognitive Function Post Stroke and is Associated with an Enhanced Cerebral Vascular Density in Female Rats.

Angiotensin signaling is known to be sexually dimorphic and although a well‐studied target for intervention in stroke and cognitive impairment in males, studies in females are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs. males, effective interventions are of utmost urgency. The aim of the current study was to determine the impact of stimulation of the angiotensin receptor subtype 2 (AT2R) with compound 21 (C21) on the development of post‐stroke cognitive impairment after experimental ischemic stroke. Ovariectomized (OVX), spontaneously hypertensive rats (SHRs) were subjected to 1 hour of middle cerebral artery occlusion (MCAO) using the suture model. At 24 hours, rats with a significant neurologic deficit were randomized to receive either saline or C21 (0.03 mg/kg/day) intraperitoneally (IP) for 5 days, then orally (0.12 mg/kg/day) for a total of 6 weeks. In a separate cohort of female SHRs, mean arterial pressure (MAP) was monitored continuously using telemetry units (Data Sciences International, St. Paul, MN). Rats were then randomized to the following treatment groups: low dose C21 (0.216 mg/kg/day, SC, Alzet Pump, Cupertino, CA), high dose C21 (0.432 mg/kg/day, SC), or surgical sham control. MAP was monitored for an additional 2 weeks. Outcomes measured were sensorimotor and cognitive function, brain structure by MRI and vascular architecture by microCT Angiography. Compound 21 preserved cognitive function, specifically spatial memory, without a significant effect on sensorimotor function or infarct size as measured by MRI. Interestingly, animals treated with C21 had a 2‐fold increase in vascular density in the ischemic hemisphere at 6 weeks, reflecting both arteriogenesis and angiogenesis. Neither low nor high dose C21 affected MAP. In conclusion, C21 prevented cognitive impairment after stroke independent of changes in MAP, likely through a mechanism involving vascular protection and restoration.Support or Funding InformationR01NS104573 to AE and SCF. Jowdy Professorship to SCF Data are mean ± SEM Saline C21 MAP (mmHg) 128±2 Low dose: 136±54# High Dose: 134±4# Bederson at Randomization 2.9 ± 0.4 2.5 ± 0.42# Bederson at 6 weeks 5 ± 0.33 N=10 5.87 ± 0.47 N =8# Infarct Size by MRI (% contralateral side) 18.74 ±1.82 N=6 14.76 ± 4.16 N=5# Sham Stroked Saline C21 Saline C21 Passive Avoidance (Latency in seconds) 276 ± 8.9, N=5 286.3 ± 3.8, N=4 91.83 ± 50.14, N=6 279 ± 5.8a, N=5 Object Placement Test (% time with moved object) 55.06 ± 4.0 N=9 45.27 ± 4.0 N=8 41.77 ± 3.72 N=10 71.6 ± 6.9a N8 MicroCT Angiography Vessel Volume/Total Volume 0.45 ± 0.08 N=4 0.51 ± 0.07 N=4 0.29 ± 0.06 N=4 0.81 ± 0.09a N=3 Vessel Number 0.04±0.007 0.04 ± 0.006 0.03 ± 0.007 0.08 ± 0.011a Vessel Thickness 0.1002± 0.007 0.1101± 0.007 0.0902± 0.007 0.0948± 0.011# Vessel Separation 1.59± 0.03 1.48 ± 0.16 1.91± 0.14 1.37± 0.12b #p&gt;0.05 vs saline, apost‐hoc Bonferoni p&lt; 0.01 vs stroke saline, bpost‐hoc Bonferoni p&lt;0.05 vs stroke saline.

P122 SEX DIFFERENCES IN STATURAL GROWTH IMPAIRMENT IN PEDIATRIC CROHN’S DISEASE: EARLY FINDINGS FROM THE GROWTH STUDY

Abstract Background Statural growth impairment is both a marker and complication of poorly controlled Crohn’s disease (CD), and occurs more commonly in males than females. The specific molecular mechanisms responsible for this sex difference in growth impairment in CD remain poorly characterized. Methods We are conducting a prospective multicenter longitudinal study (Growth Study) examining sex differences in statural growth impairment in school-age children with CD with growth potential based on bone age (BA) [females (BA 4 yrs, 2 mos to 12 years, 0 months) and males (BA 5 years, 0 months to 14 yrs, 0 mos)]. We have enrolled 118 (65% male) patients. Variable Z scores calculated based on BA are denoted as Variable BA-Z scores; those calculated based on chronological age (CA) are denoted as Variable CA-Z scores. Height Z score difference was calculated as Height CA-Z score minus Height BA-Z score. We analyzed the concentration of selected cytokines in serum in 54 patients (56% male), using a V-Plex kit (Meso Scale Discovery, Rockville, MD). Serum hormone levels were analyzed at Esoterix Endocrinology (Calabasas Hills, CA). We used t-test and Chi-squared test to examine the sex difference for continuous variables and categorical variables respectively. We assessed the association between cytokines and hormones via linear regression. Results The mean height Z score difference was -0.4 ± 1.0 (SD) [range: -3.9 to 2.0] in males and -1.1 ± 1.1 [-3.9 to 0.9] in females (Figure). The absolute value of the mean height Z score difference was significantly lower in males (P= 0.021). The mean BA Z score was (0.0 ± .04 [-0.7 to 0.9]) in males and (0.0 ± 0.2 [-0.4 to 0.5]) in females (P= 0.952). Race/ethnicity [76% White], Tanner stage [63% pre/early puberty; 37% mid/late puberty], mean disease duration [2.3 ± 1.9 (SD) (range: 0.1 to 8.3) years], medication use [65% infliximab; 39% methotrexate; 13% azathioprine/6-mercaptopurine; 9% adalimumab], and mean disease activity indices (indicated remission) did not differ by sex (P= NS for all). TNF-α, IL-4, IL-6, IL-10, and IL-12 were significantly negatively associated with hormones important in growth in males, while IL-13 was significantly negatively associated with hormones important in growth in females (Table). Conclusions Statural growth remains compromised in males compared with females in a novel contemporary cohort of children with CD. Our early data suggest that the higher frequency of growth impairment in males appears to be due to less standardized height gain with skeletal maturation, rather than advanced BA progression. BA does not appear to be significantly delayed in this cohort. Furthermore, our preliminary data suggest that systemic inflammation exerts a greater negative impact on hormone levels important in growth in males, and that different molecular pathways lead to growth impairment in males versus females. We are further investigating these preliminary findings in the ongoing prospective multicenter longitudinal Growth Study.

Caffeine consumption during development alters spine density and recovery from repetitive mild traumatic brain injury in young adult rats.

Caffeine is the most commonly used psychostimulant throughout the world, with its consumption being especially prevalent among adolescents and young adults, as over 75% of this group consumes caffeine daily. Similarly, the adolescent and young adult age group exhibit the highest incidence of traumatic brain injury (TBI). Given that both caffeine consumption and mild TBI (mTBI) are more prevalent among the late adolescent/young adult age group and that changes in dendritic spine morphology during this developmental period are poorly understood, this study sought to examine the effects of caffeine consumption during late adolescence/early adulthood on recovery from repetitive mTBI (RmTBI). The study specifically focused on changes to neuronal dendritic morphology as synaptic changes likely underlie long-term behavioral outcomes. The results demonstrate that during young adulthood caffeine consumption differentially affects the RmTBI outcomes of males and females, where the effects of caffeine and RmTBI were often additive in males while being equally detrimental, but rarely additive, in females. In general, caffeine and RmTBI induced the greatest impairments in males on cognitive and motor tasks whereas in females the most significant detriments were on pain-related tasks. Both caffeine and RmTBI increased spine density in the Cg3 (medial prefrontal cortex [mPFC]), AID (orbitofrontal cortex [OFC]), and nucleus accumbens (NAc), which is proposed to reflect an impairment in the normal pruning processes. Overall, despite caffeine's neuroprotective abilities among other age groups, this study offers concerning results regarding the detrimental effects of caffeine and RmTBI, in isolation, and especially in combination, in this susceptible population.

Impaired Bidirectional Synaptic Plasticity in Juvenile Offspring Following Prenatal Ethanol Exposure.

The hippocampus is particularly vulnerable to the teratogenic effects of prenatal ethanol exposure (PNEE), and hippocampal structural and functional deficits are thought to contribute to the learning and memory deficits that are a hallmark feature of fetal alcohol spectrum disorders. Sprague Dawley dams were exposed to a liquid diet that contained EtOH (35.5% EtOH-derived calories) throughout gestation, and then, PNEE juvenile (P21-28) male and female offspring were used for in vitro electrophysiological recordings. We examined long-term potentiation (LTP), long-term depression (LTD), and depotentiation in the medial perforant path input to the dentate gyrus (DG) to determine the impact of PNEE on the dynamic range of bidirectional synaptic plasticity in both sexes. PNEE reduced the responsiveness of the DGs of male but not in female offspring, and this effect was no longer apparent when GABAergic signaling was inhibited. There was also a sex-specific LTD impairment in males, but increasing the duration of the conditioning stimulus could overcome this deficit. The magnitude of LTP was also reduced, but in both sexes following PNEE. This appears to be an increase in the threshold for induction, not in capacity, as the level of LTP induced in PNEE animals was increased to control levels when additional conditioning stimuli were administered. These data are the first to describe, in a single study, the impact of PNEE on the dynamic range of bidirectional synaptic plasticity in the juvenile DG in both males and in females. The data suggest that PNEE increases the threshold for LTP in the DG in both sexes, but produces a sex-specific increase in the threshold for LTD in males These alterations reduce the dynamic range for synaptic plasticity in both sexes.

Elevated Serum Homocysteine Levels Have Differential Gender-Specific Associations with Motor and Cognitive States in Parkinson's Disease.

Background Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson's disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson's disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results People with Parkinson's disease displayed significantly elevated homocysteine levels (p < 0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson's disease (r s = 0.319, p < 0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson's disease (r s = −0.449, p < 0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). Conclusion Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson's disease and poorer cognitive performance in females with Parkinson's disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

Antioxidant Cocktail Acutely Restores Vascular Function After a High Sodium Meal in Males, but not Females

Endothelial dysfunction is a primary event in the development of atherosclerosis, a leading cause of cardiovascular disease (CVD). Furthermore, increased arterial stiffness is an independent risk factor for CVD. High dietary sodium intake has been shown to impair vascular function independent of blood pressure (BP) in young, healthy adults with greater impairments seen in males. A proposed mechanism of sodium‐induced vascular dysfunction is through an increase in oxidative stress. Therefore, the objective of this study was to investigate the acute effects of a high sodium meal and antioxidant cocktail on measures of vascular function and arterial stiffness. We recruited healthy, non‐hypertensive males and females 18–45 years old. Subjects completed two study visits separated by at least 48 hours and females were tested in the early follicular phase of the menstrual cycle. Vascular function was assessed using brachial artery flow‐mediated dilation (FMD) and arterial stiffness was measured by carotid‐femoral pulse wave velocity (PWV). Participants ingested either two doses of an antioxidant cocktail (AO; each capsule contained 500 mg vitamin C, 300 IU vitamin E, and 300 mg alpha‐lipoic acid) or a placebo (PLA; cellulose) followed by a high sodium meal (1500 mg Na+). BP and PWV were measured at baseline (BSL) and 30, 60, 90, and 120 minutes after meal consumption, whereas FMD at BSL, 60, and 120 min. Thirty‐four participants (14M, 20F; 23 ± 1 years; BMI 23 ± 0.4 kg/m2; systolic BP 112 ± 1 mmHg, diastolic BP 66 ± 1 mmHg) completed the study. FMD was not different between visits when all subjects were combined (AO: BSL: 6.6 ± 0.5, 60min: 6.9 ± 0.6, 120min: 6.9 ± 0.6%; PLA BSL: 7.0 ± 0.6, 60min: 6.6 ± 0.7, 120min: 6.7 ± 0.5%; P&gt;0.05). However, FMD was greater at 120min in AO compared to PLA in males (120min: AO: 6.6 ± 0.8%; PLA: 5.2 ± 0.6%; P&lt;0.05) but not in females (120min: AO: 7.2 ± 0.9%; PLA: 7.7 ± 0.6%; P&gt;0.05). Peak shear stimulus for dilation was reduced post‐meal compared to BSL in both visits in males (BSL: 758 ± 59, 60min: 657 ± 42 s−1; P&lt;0.05) but not in females (P&gt;0.05). Mean arterial pressure (MAP) was higher at 120 min compared to 60 and 90 min in both visits among all subjects (BSL: 80 ± 1, 30min: 80 ± 1, 60min: 79 ± 1, 90min: 78 ± 1, 120min: 80 ± 1mmHg, P&lt;0.05), with no differences seen among sexes (P&gt;0.05). PWV adjusted for MAP decreased from 30 to 60min and recovered from 60 to 120min for all subjects in both visits (AO: BSL: 5.4 ± 0.1, 30min: 5.4 ± 0.1, 60min: 5.3 ± 0.1, 120min: 5.5 ± 0.1 m/s; PLA: BSL: 5.2 ± 0.1, 30min: 5.3 ± 0.1, 60min: 5.1 ± 0.1, 120min: 5.3 ± 0.1 m/s; P&lt;0.05) demonstrating no effect of the AO and a similar effect was seen in males alone (BSL: 5.6 ± 0.1, 30min: 5.7 ± 0.1, 60min: 5.5 ± 0.1 m/s; P &lt;0.05), but remained unchanged in females (P&gt;0.05). There were no differences in MAP, FMD or PWV at BSL between the visits. In conclusion, vascular function was reduced following acute consumption of a high sodium meal in young, healthy males which was not observed in females. While the AO had no effect on arterial stiffness, these data suggest that AO may offer benefit to sodium‐induced vascular function impairment in males.Support or Funding InformationKAAP17S526This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluating a scale of excessive mind wandering among males and females with and without attention-deficit/hyperactivity disorder from a population sample

Recent studies highlight the role of excessive mind wandering in attention-deficit/hyperactivity disorder (ADHD) and its association with impairment. We believe assessing mind wandering could be especially relevant to individuals, including many females, who present with less externalising manifestations of ADHD. Using a new measure based on ADHD patient reports, the Mind Excessively Wandering Scale (MEWS), we previously found adults with ADHD had elevated levels of mind wandering that contributed to impairment independently of core ADHD symptoms. Using data from an online general population survey, the current study assessed the factor-structure, reliability, validity and measurement invariance of the MEWS. We also investigated sex differences in mind wandering, as well as ADHD symptoms, impairment and wellbeing in those with and without ADHD. The MEWS had a unidimensional structure, was invariant across sex, age and ADHD status, and accounted for unique variance in impairment and wellbeing beyond core ADHD symptoms. Among those with ADHD, we found no evidence for sex differences in mind wandering and among those without ADHD males had higher scores. We also found similar levels of hyperactivity/impulsivity, emotional lability, and impairment in males and females with ADHD, but males reported greater inattention and lower wellbeing. Results suggest the MEWS is a reliable and valid instrument measuring the same construct across sex, age and ADHD status, which could aid diagnosis and monitoring of outcomes.

Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice.

Fruit extract of Tribulus terrestris (TT) bears aphrodisiac and antioxidative properties. Antimicrobial drug, metronidazole (MTZ) impairs the spermatogenic activity and fertility in males. Validation of the use of fruit extract of TT as a supplement against MTZ-induced fertility impairment in males. Adult Swiss strain male mice were administered with 500mg/kgBW/day of MTZ for 28 days. Low (100mg/kgBW/day) and high (200mg/kgBW/day) doses of TT were administered simultaneously with MTZ (500mg/kgBW/day) for same duration. All males were cohabited with virgin proestrus females. Vaginal plug formation was observed to calculate the libido index. Cohabited females were sacrificed on fifteenth day of gestation to dissect out the ovaries and uteri. Fertility index, quantal pregnancy, pre-implantation and post-implantation losses were calculated. MTZ-treated males showed unaltered mating ability, however, the females impregnated by such males exhibited marked alterations in the fertility index, quantal pregnancy and pre- and post-implantation losses. Supplementation with low dose of TT failed to restore such reproductive toxicities exhibited by administration of MTZ. However, the altered reproductive toxicities were reinstated to control values following supplementation with high dose of TT. The fruit extract of TT may emerge as an effective herbal remedy, correcting the drug-induced fertility impairments in males.

Gender-related effects of vision impairment characteristics on depression in Korea

ABSTRACTPurpose: To investigate the gender-specific associations between perceived vision impairment and symptoms of depression.Methods: We used the data from the 2012 Korean Longitudinal Study of Aging database of 7448 individuals aged 45 years and older. Questionnaires assessing depression symptoms and perceived visual impairment at near, distance, and in general were administered. Logistic regression analyses were used to evaluate if visual impairment could lead to depression, adjusting for the potential confounders of age, socioeconomic status (household income, education level, marital status, and employment status), and health behaviors (alcohol consumption, smoking, and physical activity level) after gender stratification.Results: Perceived general and near vision impairment were significantly associated with symptoms of depression in males (odds ratio [OR] = 2.78 and 2.54; 95% confidence interval [CI], 1.91–4.04 and 1.78–3.63). Perceived general and distance vision impairment were significantly associated with symptoms of depression in females (OR = 2.16 and 2.08; 95% CI, 1.67–2.79 and 1.61–2.69). General sight with near vision impairment in males and general sight with distance vision impairment in females could be stronger predictors of depression than other vision impairment combinations (area under the receiver operating characteristic curve [AUROC], 0.6461; p = 0.0425 in males; AUROC, 0.6270; p = 0.0318 in females).Conclusion Gender differences were found in the characteristics of visual impairment on symptoms of depression. Ophthalmologists should be aware that near vision impairment in males and distance vision impairment in females have an adjunctive effect that might contribute to symptoms of depression.

Sexual functioning in male patients suffering from depression and anxiety disorders

IntroductionSexual dysfunctions are frequent in patients with mental illnesses. In particular, anxious and depressive symptomatology often impacts on sexual functioning.ObjectivesThe aim of this study was to evaluate the relationship between sexual function and psychological symptoms in a group of male patients with depression and anxiety disorders.MethodsFrom outpatients program, we consecutively recruited a group of 46 males: 28 patients had major depression and 18 anxiety disorders. Then, we administered two self-report psychometric tools to assess male sexuality, depression and anxiety, i.e., international index of erectile function (IIEF-15), and Depression Anxiety Stress Scales (DASS-21). t-tests and Pearson correlations were performed.ResultsWe found significantly higher score in terms of desire and general sexual wellness in people with anxiety disorder compared to people with depression. However, we found more significant correlations among depressive/anxious symptomatology and sexual impairment in males with anxiety disorders compared to males with depression.ConclusionsOur results revealed that males diagnosed with depression show a decrease of sexual desire, as a vast part of literature previously affirmed. On the contrary, the relationship between psychological symptomatology and sexual dysfunction, as the reduction of erectile function, was higher in males with anxiety disorders. This difference is probably due to a major iatrogenic effect of antidepressive treatments in depressed patients, while in anxious patients could be the psychological state, per se, the main cause of sexual dysfunctions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Sex bias in autism spectrum disorder in neurofibromatosis type 1

BackgroundDespite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism.MethodsWe analysed data from n = 194 children aged 4–16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires.ResultsThere was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire.ConclusionsThere is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD.

Association of hearing impairment with insulin resistance, β-cell dysfunction and impaired fasting glucose before onset of diabetes.

Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance (IR), β-cell dysfunction and impaired fasting glucose (IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population. Participants included 1589 males and 2496 females, who were ≥ 20 years of age and without diabetes from the Korea National Health and Nutritional Examination Surveys of the Korean population (2010). Audiometric tests and laboratory examinations were performed. Homeostasis model assessments of IR and β-cell function (HOMA-IR and HOMA-β) were calculated. The prevalence of both high- and low-/mid-frequency hearing impairment among subjects with IFG was higher compared with those with normal glycaemia (42.2% vs. 24.5%, 14.7% vs. 7.8%, respectively). After adjustment for age, HOMA-IR and HOMA-β showed significant association with high-frequency hearing impairment in males. In the multiple logistic regression analyses adjusting for confounding variables, the presence of IFG, higher HOMA-IR and lower HOMA-β remained as independent risk factors for high-frequency mild hearing impairment in males < 70 years [odds ratio (OR) 1.441, 95% confidence interval (95% CI), 1.056 to 1.967; OR, 1.448, 95% CI, 1.039 to 2.101; and OR, 0.447, 95% CI, 0.274 to 0.729, P < 0.05, respectively). IR, β-cell dysfunction and IFG are associated with high-frequency mild hearing impairment in the male population < 70 years before the onset of diabetes.

Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring

Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.