Browsing by Subject "sex differences"

Now showing 1 - 6 of 6
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    Alpha synuclein functions as a sex-specific modulator of cognition and gene expression
    (2022-12) Brown, Jennifer
    Neurodegenerative diseases such as Alzheimer’s and Parkinson’s impact large portions of the population. Though such diseases have distinguishing features, they also often share pathology and symptomology. Alpha synuclein (αSyn; gene SNCA) is a protein commonly found in a range of neurodegenerative conditions. αSyn can interact with tau and amyloid-beta to modulate disease phenotypes, but its normal functions remain incompletely characterized. To explore the contribution of αSyn to Alzheimer’s disease, I first asked whether reducing αSyn in a mouse model of Alzheimer’s would improve cognition. Using a translationally relevant strategy, the reduction of αSyn reveled a sex-specific effect whereby male, but not female, mice showed improved spatial memory. Follow-up studies with constitutive SNCA knockout mice revealed a previously unreported female-specific deficit in spatial learning and memory. Next, we utilized electrophysiology, immunofluorescence imaging and transcriptomics to elucidate potential mechanisms underlying this effect. Results revealed a novel impairment in long-term potentiation, as well as differential expression of genes related to learning and immune function in female mice in response to SNCA ablation. These results not only describe a novel sex-specific function of αSyn, but provide translationally-relevant information regarding the potential effects of using αSyn reduction as a therapeutic strategy for neurodegenerative conditions.
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    Antidepressant Effects of TRH Analogue EEP in Female and Male Rats Assessed with the Forced Swim Test and BDNF Assay
    (2023-05) Schulz, Emily N
    The endogenous peptide pGLU-GLU-PRO-NH2 (EEP) has antidepressant effects in male rats demonstrated by decreased immobility in the forced swim test (FST). EEP is a chemical analog of thyrotropin-releasing hormone (TRH), which has short-term antidepressant effects by intrathecal administration in humans. In people with depression, brain-derived neurotrophic factor (BDNF) is decreased in the hippocampus and frontal cortex which leads to decreased volume in both. When people are successfully treated for depression, irrespective of the treatment type, BDNF and volume increase in the hippocampus and frontal cortex, which can indicate recovery. Sex differences are present in the occurrence and symptoms of depression; however, female animals are not always represented in depression research. Female sex hormones are thought to be a reason for sex differences related to depression, and BDNF is known to fluctuate over the estrous cycle of female rats. This study sought to determine if the antidepressant effects of EEP are related to BDNF levels in rats. This study found no significant effects with the forced swim test (FST) and immobility but had a large effect size. A minor sex difference was present in the FST (p = 0.03). Rats that received EEP were not found to have significantly increased levels of BDNF in the hippocampus and frontal cortex, but the results had a large effect size with the frontal cortex. No sex difference was found with BDNF concentrations. Results related to the estrous cycle were insignificant and considered exploratory. The results suggest that continued testing of EEP is needed to gain a greater understanding.
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    Perceiving affordances for receiving a serve in virtual volleyball
    (2024-04) Arruda, Danilo
    Affordances are opportunities for action that are available for a given person in a given environment. When receiving serves in volleyball, players commonly use one of two techniques; overhead (hands pronated above the head) or underhand (hands supinated near the waist). The relative utility of those techniques is influenced by characteristics of each serve, including its height. At the same time, the importance of serve height varies with the height of the player. This relationship suggests that it might be possible (and useful) to consider serve reception in volleyball in the context of affordances. Using a head-mounted virtual reality system, I varied the height of incoming serves, ranging from 1 m to 2.25 m. Participants responded to each serve by attempting to intercept it using either the overhead or underhand technique. I predicted that participants (skilled volleyball players) would use the overhead technique for higher serves and the underhand technique for lower serves, and that there would be discrete transition between the two techniques, consistent with the hypothesis that players perceive incoming serves in terms of whether they afford one or the other technique. I varied the height of participants by utilizing players from men’s and women’s volleyball teams. I separately analyzed the choice of serve reception techniques in terms of serve height expressed extrinsically (i.e., in meters) and expressed intrinsically (i.e., in relation to each participant’s maximum vertical reach). These separate analyses made it possible for me to identify possible sex differences in serve reception that were related to sex differences in height, as well as differences in serve reception technique that were not related to sex differences in height. I also analyzed data about displacement of the VR headset and used those data as a measure of whole-body movement as participants prepared to receive each serve. As predicted, I found discrete transitions between techniques, in relation to serve height. Separately, I found evidence for sex differences in serve reception that were related to sex differences in height, but also others that were not related to sex differences in height. Finally, I found systematic relationships between serve height, patterns of whole-body anticipatory movement, and use of the overhead and underhand techniques. I interpreted those relationships as evidence for the perception of higher order affordances for the use of anticipatory whole-body movement to optimize the utility of particular serve reception techniques. I concluded 1) that incoming serves in volleyball can be perceived in terms of their affordances, 2) that head-mounted virtual reality is a useful method for the study of affordance perception in time-constrained domains, such as volleyball, 3) that sex differences in volleyball arise from anthropometric sex differences but also from sex differences that are not related to anthropometrics, and 4) that skilled volleyball players can perceive incoming serves in terms of higher order affordances in which anticipatory movements are relative to techniques for serve reception.
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    Sex differences and flexible decision making behavior in a mouse model of 16p11.2 hemideletion
    (2023) Merfeld, Madison
    Compared with girls and women, boys and men have a higher rate of diagnosis and/or a greater level of impairment associated with neurodevelopmental conditions such as autism spectrum disorders and attention deficit hyperactivity disorder (ADHD). We know little about how sex mechanisms influence the impact of diagnosis-associated gene variants; one gene variant strongly associated with neurodevelopmental disorders is 16p11.2 hemideletion. Boys with 16p11.2 hemideletion have been repeatedly found to have more neurodevelopmental diagnoses than girls. The 16p11.2 region is highly syntenic across mammals, and mouse models of 16p11.2 hemideletion (abbreviated as 16p del) also show sex-biased impacts on flexible action selection. In a restless two-armed bandit decision making, I found that 16p del mice have sex-biased behavioral changes in the domain of flexible action selection.
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    Sex Differences, Physiological Response, and Emotion
    (2022-06) Baumann, Ashley M
    Females have a higher prevalence for PTSD and other anxiety disorders than males, thus fluctuating sex hormones, such as estrogen, are considered to play a role. Research suggests that during predictable cue tasks, high estrogen females had greater startle response toward predictable tasks compared to unpredictable and control tasks. The current study used physiological responses and self-reported measures to investigate fear response during the oddball task within naturally and unnaturally cycling females. The oddball task consisted of five time points, consistent with control, unpredictable, predictable, extinction, and control blocks. Participants viewed a randomized slide show of three visual stimuli consisting of natural and control images. Participants (n = 26) were split into high or low estrogen groups and were placed in a separate group if using a hormonal contraceptive. Results found that, overall, participants had a greater positive affect at time two than at time five, F(4,80) = 3.832, p = .007. Given the small sample size, a second set of analyses assessed high estrogen level females and those using hormonal contraceptive (lower estrogen) after time the first control (time two) and after the unpredictable and predictable block (time three). Results found between group differences in state anxiety, such that HC females had greater state anxiety than the high estrogen group, F(1,12) = 4.880 , p = .047. These results were opposite for our hypotheses that overall, females with high estrogen levels will have greater self-reported mood, anxiety, and physiological response across the study. Results also opposed our hypothesis such that a group by time interaction revealed participants in the HC group had significantly higher positive affect at time two which decreased at time three, F(1,12) = 4.931, p = .046; This significant difference between time points occurred only in participants using HC.
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    Sex-correlated variability in exploration strategy in uncertain environments
    (2022-07) Chen, Sijin 'Cathy'
    Every organism must balance between two goals: exploiting rewarding options when they are available and exploring more new information about potential better alternatives. Adaptively transition between exploration and exploitation is essential when navigating an uncertain world. Exploration is dysregulated in numerous neuropsychiatric disorders, many of which are sex-biased in risk, presentation, and prognosis. This raises the possibility that sex-linked mechanisms could modulate exploration differently and contribute to sex-linked individual variability in the vulnerability or resilience to these conditions. Understanding how individuals explore uncertain environments can give us in sight into how brains implement divergent exploration strategy. In this dissertation, I present three studies investigating 1. exploration strategy in a complex novel environment, 2. exploration strategy in a changing environment, 3. neuromodulatory systems underlying exploration strategy. In experiment 1 and 2, I observed a spectrum of strategies that individuals adopted to navigate the environment and sex captured a major source of variability in the strategies adopted. Both sexes did not differ in the ability to learn the task but they differed in the preferred strategy employed to explore an uncertain environment. Females preferred a more energy-conserving, systematic and exploitative approach across both tasks, where as males predominantly used more variable and exploratory approach. In experiment 3, I modulated tonic dopamine and norepinephrine level and examined the modulatory effect on exploration. The results suggested novel role of dopamine in mediating exploration and highlighted the sex-differentiated modulatory effect of norepinephrine on exploration. This dissertation took advantage of computational tools and revealed sex-correlated variability in strategies employed when interacting with an uncertain environment, rather than any difference in ability. This highlighted sex as source of individual variability and implicated potential sex-modulated circuits and systems that could contribute to vulnerability or risk for neuropsychiatric disorders.