Browsing by Subject "Females"

Now showing 1 - 7 of 7
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    Activation of extrasynaptic δ-GABAA receptors globally or within the posterior-VTA has estrous-dependent effects on consumption of alcohol and estrous-independent effects on locomotion
    (Elsevier, 2017-09) Melón, Laverne C.; Nolan, Zachary T.; Colar, Delphine; Moore, Eileen M.; Boehm II, Stephen L.; Psychology, School of Science
    Recent reports support higher than expected rates of binge alcohol consumption among women and girls. Unfortunately, few studies have assessed the mechanisms underlying this pattern of intake in females. Studies in males suggest that alcohol concentrations relevant to the beginning stages of binge intoxication may selectively target tonic GABAergic inhibition mediated by GABAA receptor subtypes expressing the δ-subunit protein (δ-GABAARs). Indeed, administration of agonists that interact with these δ-GABAARs prior to alcohol access can abolish binge drinking behavior in male mice. These δ-GABAARs have also been shown to exhibit estrous-dependent plasticity in regions relevant to drug taking behavior, like the hippocampus and periaqueductal gray. The present experiments were designed to determine whether the estrous cycle would alter binge drinking, or our ability to modulate this pattern of alcohol use with THIP, an agonist with high selectivity and efficacy at δ-GABAARs. Using the Drinking-in-the-Dark (DID) binge-drinking model, regularly cycling female mice were given 2h of daily access to alcohol (20%v/v). Vaginal cytology or vaginal impedance was assessed after drinking sessions to track estrous status. There was no fluctuation in binge drinking associated with the estrous cycle. Both Intra-posterior-VTA administration of THIP and systemic administration of the drug was also associated with an estrous cycle dependent reduction in drinking behavior. Pre-treatment with finasteride to inhibit synthesis of 5α-reduced neurosteroids did not disrupt THIP's effects. Analysis of δ-subunit mRNA from posterior-VTA enriched tissue samples revealed that expression of this GABAA receptor subunit is elevated during diestrus in this region. Taken together, these studies demonstrate that δGABAARs in the VTA are an important target for binge drinking in females and confirm that the estrous cycle is an important moderator of the pharmacology of this GABAA receptor subtype.
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    Centering F.a.M.I.L.Y in Black Girls' STEM Learning. Equity by Design
    (Midwest and Plains Equity Assistance Center, 2022) Morton, Crystal; Palmer-Azikiwe, Chanae; Barlow, Marva Renee
    In this "Equity by Design" brief, the authors describe the F.a.M.I.L.Y (Fostering and Maximizing Interdisciplinary Learning Year-round) Project and discuss the Project's importance and impact on Black girls and their caregivers. The brief ends with a discussion of strategies implemented during the F.a.M.I.L.Y Project to create a holistic and inclusive environment for STEM learning and positive STEM identity development.
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    Dystrophic spinal deformities in a neurofibromatosis type 1 murine model
    (PLoS, 2015-03-18) Rhodes, Steven D.; Zhang, Wei; Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiahoua; Yang, Xianlin; Mohammad, Khalid S.; Guise, Theresa A.; Bergner, Amanda L.; Stevenson, David A.; Yang, Feng-Chun; Department of Anatomy and Cell Biology, IU School of Medicine
    Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.
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    Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner
    (BioMed Central, 2015-09-18) Ikeda, Mizuko; Swide, Thomas; Vayl, Alexandra; Lahm, Tim; Anderson, Anderson; Hutchens, Michael P.; Department of Medicine, IU School of Medicine
    INTRODUCTION: There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR. METHODS: CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17β-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting. RESULTS: Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females. CONCLUSIONS: Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal ERs. Post-arrest estrogen administration is renoprotective in a sex- and age-dependent manner.
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    Prediction of Radiation Esophagitis in Non-Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels
    (Elsevier, 2018-02) Hawkins, Peter G.; Boonstra, Philip S.; Hobson, Stephen T.; Hayman, James A.; Ten Haken, Randall K.; Matuszak, Martha M.; Stanton, Paul; Kalemkerian, Gregory P.; Lawrence, Theodore S.; Schipper, Matthew J.; Kong, Feng-Ming (Spring); Jolly, Shruti; Radiation Oncology, School of Medicine
    Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non-small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.
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    Sex differences in specific aspects of two animal tests of anxiety-like behavior
    (Springer, 2021) De Oliveira Sergio, Thatiane; Wetherill, Leah; Kwok, Claudina; Khoyloo, Farrah; Hopf, Frederic W.; Psychiatry, School of Medicine
    Rationale: Anxiety, a negative state of high arousal and vigilance, is especially prevalent in women, making identification of underlying mechanisms critical for developing effective therapies. With the challenge of disentangling biological and social factors in humans, animal tests can provide valuable insights, although such tests, developed in males, have unclear validity for females. Objective: To better understand patterns of sex differences across multiple measures within two classical rodent anxiety tests. Methods: We examined female and male adult Wistar rats (n = 15-18/group) that were single-housed in the novelty suppression of feeding test (NSFT) that involves food under a bright light in food-restricted animals, and light-dark test (LDT), which reflects innate aversion to bright light. To further validate these tests in females, we also examined the impact of 1 mg/kg diazepam. Results: NSFT measures of the most direct interaction with food, latency to grab food and food consumed, indicated increased anxiety-like behavior in females versus males, with diazepam altering these behaviors in females but not males. Most other measures showed more similar effects of diazepam across the sexes, with some evidence of reduced anxiety-like behavior in LDT for females. Principal component analyses indicated limited relationships across behavioral factors, underscoring previous suggestions of the importance of assessing multiple measures to maximize information and ethological relevance. Conclusions: Combining our findings and previous studies, we speculate that increased anxiety-like behavior in females manifests especially when there is a specific, life-relevant condition (e.g., food in the NSFT). Our findings also validate NSFT and LDT use in females.
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    The Slow Work of Democracy: Resisting Reductionist Views of Women and Children
    (Lewis & Clark, 2017) Serriere, Stephanie C.
    In her research article "State your defense!": Children negotiate analytic frames in the context of deliberative dialogue," Hauver offers important contributions to the field of elementary civic education that illuminate how young people apply various analytical frames to make collective decisions. First, I highlight significant contributions of her work, namely children's capabilities to build perspective-taking through dialogue, which I suggest can be more solidly grounded in a sociocultural framework, not a developmental one. Second, I offer suggestions toward such a theoretical framework that loosens determinism for children's development and offers a less deterministic framework for women. My review seeks to amplify Hauver's important findings by suggesting more theoretical cohesion as well as more contemporary and critical frameworks. [For "'State Your Defense!' Children Negotiate Analytic Frames in the Context of Deliberative Dialogue," see EJ1162608.]