Browsing by Subject "sex differences"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Dietary nitrate‐induced increases in human muscle power: high versus low responders
    (Wiley, 2018-01-25) Coggan, Andrew R.; Broadstreet, Seth R.; Mikhalkova, Deana; Bole, Indra; Leibowitz, Joshua L.; Kadkhodayan, Ana; Park, Soo; Thomas, Deepak P.; Thies, Dakkota; Peterson, Linda R.; Kinesiology, School of Health and Human Sciences
    Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO 3 −), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22–79 year of age and weighing 52.1–114.9 kg were studied using a randomized, double‐blind, placebo‐controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO 3 −. Plasma NO 3 − and nitrite (NO 2 −) were measured as indicators of NO bioavailability and maximal knee extensor speed (V max), power (P max), and fatigability were determined via isokinetic dynamometry. On average, dietary NO 3 − increased (P < 0.05) P max by 4.4 ± 8.1%. Individual changes, however, ranged from −9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO 3 − dose per kg), body mass index (surrogate for body composition) or placebo trial V max or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO 2 − concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO 3 −‐induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO 2 − and possibly female sex.
  • Thumbnail Image
    Item
    Differential COMT expression and behavioral effects of COMT inhibition in male and female Wistar and alcohol preferring rats
    (Elsevier, 2017) McCane, Aqilah M.; DeLory, Michael J.; Timm, Maureen M.; Janetsian-Fritz, Sarine S.; Lapish, Christopher C.; Czachowski, Cristine L.; Department of Psychology, School of Science
    Polymorphisms of the catechol-O-methyl transferase (COMT) gene have been associated with alcoholism, suggesting that alterations in the metabolism of catecholamines may be a critical component of the neuropathology of alcoholism. In the current experiments, the COMT inhibitor tolcapone was utilized in an operant behavioral model of reinforcer-seeking and drinking to determine if this compound was capable of remediating the excessive seeking and drinking phenotype of the alcohol-preferring P rat. Tolcapone was administered to male and female alcohol-reinforced P and Wistar rats. Additionally, tolcapone was administered to male sucrose-reinforced P and Wistar rats to determine if its effects also extended to a natural reinforcer. Animals were trained to make an operant response that resulted in 20 min uninterrupted access to the reinforcer solutions. Tolcapone had no effect in female rats on either seeking or consumption of ethanol. However, reductions of both reinforcer seeking and consumption were observed in male P rats, but only of seeking in Wistars. In separate experiments, using reinforcer naïve male and female animals, COMT expression was assessed via Western Blot analysis. Sex differences in COMT expression were also observed, where male P rats exhibited a marked reduction in protein expression relative to females in the PFC. Sex differences were not observed for Wistars or in the striatum and hippocampus. These data complement our previous findings in which tolcapone reduced cue-evoked responses in P rats and further suggest clinical utility of COMT inhibitors in the treatment of addiction disorders, specifically in male high drinkers.
  • Thumbnail Image
    Item
    Greater male than female variability in regional brain structure across the lifespan
    (Wiley, 2021) Wierenga, Lara M.; Doucet, Gaelle E.; Dima, Danai; Agartz, Ingrid; Aghajani, Moji; Akudjedu, Theophilus N.; Albajes‐Eizagirre, Anton; Alnæs, Dag; Alpert, Kathryn I.; Andreassen, Ole A.; Anticevic, Alan; Asherson, Philip; Banaschewski, Tobias; Bargallo, Nuria; Baumeister, Sarah; Baur‐Streubel, Ramona; Bertolino, Alessandro; Bonvino, Aurora; Boomsma, Dorret I.; Borgwardt, Stefan; Bourque, Josiane; Braber, Anouk; Brandeis, Daniel; Breier, Alan; Brodaty, Henry; Brouwer, Rachel M.; Buitelaar, Jan K.; Busatto, Geraldo F.; Calhoun, Vince D.; Canales‐Rodríguez, Erick J.; Cannon, Dara M.; Caseras, Xavier; Castellanos, Francisco X.; Chaim‐Avancini, Tiffany M.; Ching, Christopher R. K.; Clark, Vincent P.; Conrod, Patricia J.; Conzelmann, Annette; Crivello, Fabrice; Davey, Christopher G.; Dickie, Erin W.; Ehrlich, Stefan; Ent, Dennis; Fisher, Simon E.; Fouche, Jean‐Paul; Franke, Barbara; Fuentes‐Claramonte, Paola; Geus, Eco J. C.; Di Giorgio, Annabella; Glahn, David C.; Gotlib, Ian H.; Grabe, Hans J.; Gruber, Oliver; Gruner, Patricia; Gur, Raquel E.; Gur, Ruben C.; Gurholt, Tiril P.; Haan, Lieuwe; Haatveit, Beathe; Harrison, Ben J.; Hartman, Catharina A.; Hatton, Sean N.; Heslenfeld, Dirk J.; Heuvel, Odile A.; Hickie, Ian B.; Hoekstra, Pieter J.; Hohmann, Sarah; Holmes, Avram J.; Hoogman, Martine; Hosten, Norbert; Howells, Fleur M.; Hulshoff Pol, Hilleke E.; Huyser, Chaim; Jahanshad, Neda; James, Anthony C.; Jiang, Jiyang; Jönsson, Erik G.; Joska, John A.; Kalnin, Andrew J.; Karolinska Schizophrenia Project (KaSP) Consortium; Klein, Marieke; Koenders, Laura; Kolskår, Knut K.; Krämer, Bernd; Kuntsi, Jonna; Lagopoulos, Jim; Lazaro, Luisa; Lebedeva, Irina S.; Lee, Phil H.; Lochner, Christine; Machielsen, Marise W. J.; Maingault, Sophie; Martin, Nicholas G.; Martínez‐Zalacaín, Ignacio; Mataix‐Cols, David; Mazoyer, Bernard; McDonald, Brenna C.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Katie L.; McPhilemy, Genevieve; Meer, Dennis; Menchón, José M.; Naaijen, Jilly; Nyberg, Lars; Oosterlaan, Jaap; Paloyelis, Yannis; Pauli, Paul; Pergola, Giulio; Pomarol‐Clotet, Edith; Portella, Maria J.; Radua, Joaquim; Reif, Andreas; Richard, Geneviève; Roffman, Joshua L.; Rosa, Pedro G. P.; Sacchet, Matthew D.; Sachdev, Perminder S.; Salvador, Raymond; Sarró, Salvador; Satterthwaite, Theodore D.; Saykin, Andrew J.; Serpa, Mauricio H.; Sim, Kang; Simmons, Andrew; Smoller, Jordan W.; Sommer, Iris E.; Soriano‐Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Szeszko, Philip R.; Temmingh, Henk S.; Thomopoulos, Sophia I.; Tomyshev, Alexander S.; Trollor, Julian N.; Uhlmann, Anne; Veer, Ilya M.; Veltman, Dick J.; Voineskos, Aristotle; Völzke, Henry; Walter, Henrik; Wang, Lei; Wang, Yang; Weber, Bernd; Wen, Wei; West, John D.; Westlye, Lars T.; Whalley, Heather C.; Williams, Steven C. R.; Wittfeld, Katharina; Wolf, Daniel H.; Wright, Margaret J.; Yoncheva, Yuliya N.; Zanetti, Marcus V.; Ziegler, Georg C.; Zubicaray, Greig I.; Thompson, Paul M.; Crone, Eveline A.; Frangou, Sophia; Tamnes, Christian K.; Psychiatry, School of Medicine
    For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
  • Thumbnail Image
    Item
    Impact of Sex and Antihypertensive Medication on Global Cognition in Primary Care Older Adults
    (Oxford, 2022-11) de la Colina, Adrian Noriega; Vasiliadis, Helen-Maria; Berbiche, Djamal; Bherer, Louis; Girouard, Helene; Kaushal, Navin; Health Sciences, School of Health and Human Sciences
    Hypertension is one of the strongest modifiable risk factors for the development of cognitive impairment and dementia. However, there are conflicting reports regarding which class of antihypertensive medication is the best for reducing the risk of cognitive decline. The objective of this study is to determine whether sex determines the pharmacological therapy that is the most effective in preserving cognitive outcomes. This study examined 1607 participants from the ESA Services Study, a longitudinal survey of older adults over 65 years old in Quebec-Canada. They were examined for the Mini-Mental State Examination(MMSE) at baseline (T1) and followed up three (T2) and four years after (T3). Hypertensive women had the highest mean MMSE score at each time point (T1 28.591 (SE .064); T2 28.282 (SE .118); T3 28.524 (SE.119)), while hypertensive men had the worst (T1 28.038(SE.070); T2 27.694(SE.125); 27.809(SE.128)). Women taking angiotensin II receptor antagonists (ARBs) showed the highest MMSE scores (p<.003), and men taking diuretics and other antihypertensives had the lowest MMSE scores(p<.001) after a 3-year follow-up. Combination therapy of two or three antihypertensives drugs was associated with higher scores in women at T1 and T2 (p<.001). In men, taking three antihypertensives showed a sharp decrease in MMSE scores from T1 to T3 (p<.001). Sex differences in global cognition outcomes in older adults are in part due to the heterogeneity in effects related to the type and number of antihypertensive drugs used. Effective antihypertensive treatment should consider the impact of sex to optimize the effect of pharmacological interventions on cognition.
  • Thumbnail Image
    Item
    Sex differences in cardiovascular risk profiles of ischemic stroke patients with diabetes in the Greater Cincinnati/Northern Kentucky Stroke Study
    (Wiley, 2017) Madsen, Tracy E.; Khoury, Jane C.; Alwell, Kathleen A.; Moomaw, Charles J.; Demel, Stacie L.; Flaherty, Matthew L.; Woo, Daniel; Mackey, Jason; De Los Rios La Rosa, Felipe; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Kissela, Brett M.; Kleindorfer, Dawn O.; Department of Neurology, School of Medicine
    Background The aim of the present study was to compare sex-specific associations between cardiovascular risk factors and diabetes mellitus (DM) among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). Methods The GCNKSS ascertained AIS cases in 2005 and 2010 among adult (age ≥ 20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors were compared between those with and without DM using Chi-squared tests and multiple logistic regression analysis to examine sex-specific profiles. Results There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were Black, and 1146 (33%) had DM. Among both women and men with DM, significantly more were obese and had hypertension, high cholesterol, and coronary artery disease (CAD) compared with those without DM. For women with AIS, multivariable sex-specific adjusted analyses revealed that older age was associated with decreased odds of having DM (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.80–0.98). For women with CAD, the odds of DM were increased (aOR 1.76, 95% CI 1.33–2.32). Age and CAD were not significant factors in differentiating the profiles of men with and without DM. Conclusions Women with DM had strokes at a younger age, whereas no such age difference existed in men. Compared with men, women with DM were also more likely to have CAD than those without DM, suggesting a sex difference in the association between DM and vascular disease. These findings may suggest a need for more aggressive risk factor management in diabetic women.
  • Thumbnail Image
    Item
    Skeletal muscle contraction kinetics and AMPK responses are modulated by the adenine nucleotide degrading enzyme AMPD1
    (American Physiological Society, 2022-11) Hafen, Paul S.; Law, Andrew S.; Matias, Catalina; Miller, Spencer G.; Brault, Jeffrey J.; Anatomy, Cell Biology and Physiology, School of Medicine
    AMP deaminase 1 (AMPD1; AMP → IMP + NH3) deficiency in skeletal muscle results in an inordinate accumulation of AMP during strenuous exercise, with some but not all studies reporting premature fatigue and reduced work capacity. To further explore these inconsistencies, we investigated the extent to which AMPD1 deficiency impacts skeletal muscle contractile function of different muscles and the [AMP]/AMPK responses to different intensities of fatiguing contractions. To reduce AMPD1 protein, we electroporated either an inhibitory AMPD1-specific miRNA encoding plasmid or a control plasmid, into contralateral EDL and SOL muscles of C57BL/6J mice (n = 48 males, 24 females). After 10 days, isolated muscles were assessed for isometric twitch, tetanic, and repeated fatiguing contraction characteristics using one of four (None, LOW, MOD, and HIGH) duty cycles. AMPD1 knockdown (∼35%) had no effect on twitch force or twitch contraction/relaxation kinetics. However, during maximal tetanic contractions, AMPD1 knockdown impaired both time-to-peak tension (TPT) and half-relaxation time (½ RT) in EDL, but not SOL muscle. In addition, AMPD1 knockdown in EDL exaggerated the AMP response to contractions at LOW (+100%) and MOD (+54%) duty cycles, but not at HIGH duty cycle. This accumulation of AMP was accompanied by increased AMPK phosphorylation (Thr-172; LOW +25%, MOD +34%) and downstream substrate phosphorylation (LOW +15%, MOD +17%). These responses to AMPD1 knockdown were not different between males and females. Our findings demonstrate that AMPD1 plays a role in maintaining skeletal muscle contractile function and regulating the energetic responses associated with repeated contractions in a muscle- but not sex-specific manner. NEW & NOTEWORTHY AMP deaminase 1 (AMPD1) deficiency has been associated with premature muscle fatigue and reduced work capacity, but this finding has been inconsistent. Herein, we report that although AMPD1 knockdown in mouse skeletal muscle does not change maximal isometric force, it negatively impacts muscle function by slowing contraction and relaxation kinetics in EDL muscle but not SOL muscle. Furthermore, AMPD1 knockdown differentially affects the [AMP]/AMPK responses to fatiguing contractions in an intensity-dependent manner in EDL muscle.