Scholarly Works, Human Nutrition, Foods, and Exercise

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Research articles, presentations, and other scholarship


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  • Editorial: Effects of performing arts training on the brain, (socio)cognitive and motor functions across the lifespan
    Kausel, Leonie; Basso, Julia C.; Grinspun, Noemí; Alain, Claude (Frontiers Media, 2023-12-06)
    Performing arts are a cultural expression that is ubiquitous around the world and consists of arts that are performed for an audience, such as music, dance, and drama. In recent years, there has been a growing interest in understanding how this expressive, and in essence social activity, impacts brain development and plasticity. This topic aimed to collect evidence on how the brain and (socio)cognitive and motor functions are influenced by performing arts training along the lifespan, deepening the current knowledge on this subject and helping to unravel the neurobiological mechanisms that underlie these changes. The five articles presented in this Research Topic explore research on an acting intervention, cover matters related to dance training, identify variables related to music sophistication, and focus on performing arts and musical training.
  • Dissociation and other trauma symptomatology are linked to imbalance in the competing neurobehavioral decision systems
    Basso, Julia C.; Satyal, Medha K.; McKee, Kevin L.; Lynn, Sarah; Gyamfi, Daphne; Bickel, Warren K. (Frontiers Media, 2024-01-31)
    Objective: Dissociation is a conscious state characterized by alterations in sensation and perception and is thought to arise from traumatic life experiences. Previous research has demonstrated that individuals with high levels of dissociation show impairments in cognitive-emotional processes. Therefore, using the Competing Neurobehavioral Decisions System (CNDS) theory, we used statistical modeling to examine whether dissociative experience and trauma symptoms are independently predicted by impulsivity, risk-seeking, affective state (i.e., anxiety, depression, stress, and negative affect), and trauma history. Method: In this cross-sectional study design, data were collected via Amazon Mechanical Turk from a total of n = 557 English-speaking participants in the United States. Using Qualtrics, participants answered a series of self-reported questionnaires and completed several neurocognitive tasks. Three independent multiple linear regression models were conducted to assess whether impulsivity, risk seeking, affective state, and trauma history predict depersonalization, trauma symptoms, and PTSD symptoms. Results: As hypothesized, we found that depersonalization and other trauma symptoms are associated with heightened impulsivity, increased risk-seeking, impaired affective states, and a history of traumatic experiences. Conclusion: We demonstrate that an imbalanced CNDS (i.e., hyperimpulsive/ hypoexecutive), as evidenced by decreased future valuation, increased risk seeking, and impaired affective states, predicts heightened depersonalization and other trauma and PTSD symptomatology. This is the first time that dissociation has been connected to delay discounting (i.e., the tendency to place more value on rewards received immediately compared to farther in the future). Interventions that positively impact areas of the CNDS, such as episodic future thinking or mindfulness meditation, may be a target to help decrease dissociative symptoms.
  • Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations dynamically coupled with hippocampal rhythms across brain states
    Arndt, Kaiser C.; Gilbert, Earl T.; Klaver, Lianne M.F.; Kim, Jongwoon; Buhler, Chelsea M.; Basso, Julia C.; McKenzie, Sam; English, Daniel Fine (CellPress, 2024-03-26)
    The granular retrosplenial cortex (gRSC) exhibits high-frequency oscillations (HFOs; ~150 Hz), which can be driven by a hippocampus-subiculum pathway. How the cellular-synaptic and laminar organization of gRSC facilitates HFOs is unknown. Here, we probe gRSC HFO generation and coupling with hippocampal rhythms using focal optogenetics and silicon-probe recordings in behaving mice. ChR2-mediated excitation of CaMKII-expressing cells in L2/3 or L5 induces HFOs, but spontaneous HFOs are found only in L2/3, where HFO power is highest. HFOs couple to CA1 sharp wave-ripples (SPW-Rs) during rest and the descending phase of theta. gRSC HFO current sources and sinks are the same for events during both SPW-Rs and theta oscillations. Independent component analysis shows that high gamma (50–100 Hz) in CA1 stratum lacunosum moleculare is comodulated with HFO power. HFOs may thus facilitate interregional communication of a multisynaptic loop between the gRSC, hippocampus, and medial entorhinal cortex during distinct brain and behavioral states.
  • Examining the Effect of Increased Aerobic Exercise in Moderately Fit Adults on Psychological State and Cognitive Function
    Basso, Julia C.; Oberlin, Douglas J.; Satyal, Medha K.; O’Brien, Catherine E.; Crosta, Christen; Psaras, Zach; Metpally, Anvitha; Suzuki, Wendy A. (Frontiers Media, 2022-07-12)
    Regular physical exercise can decrease the risk for obesity, diabetes, and cardiovascular disease, increase life expectancy, and promote psychological health and neurocognitive functioning. Cross-sectional studies show that cardiorespiratory fitness level (VO₂ max) is associated with enhanced brain health, including improved mood state and heightened cognitive performance. Interventional studies are consistent with these cross-sectional studies, but most have focused on low-fit populations. Few such studies have asked if increasing levels of physical activity in moderately fit people can significantly enhance mood, motivation, and cognition. Therefore, the current study investigated the effects of increasing aerobic exercise in moderately fit individuals on psychological state and cognitive performance.We randomly assigned moderately fit healthy adults, 25–59 years of age, who were engaged in one or two aerobic exercise sessions per week to either maintain their exercise regimen (n = 41) or increase their exercise regimen (i.e., 4–7 aerobic workouts per week; n = 39) for a duration of 3 months. Both before and after the intervention, we assessed aerobic capacity using a modified cardiorespiratory fitness test, and hippocampal functioning via various neuropsychological assessments including a spatial navigation task and the Mnemonic Similarity Task as well as self-reported measures including the Positive and Negative Affect Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, Perceived Stress Scale, Rumination Scale, Eating Disorders Examination, Eating Attitudes Test, Body Attitudes Test, and Behavioral Regulation of Exercise Questionnaire. Consistent with our initial working hypotheses, we found that increasing exercise significantly decreased measures of negative affect, including fear, sadness, guilt, and hostility, as well as improved body image. Further, we found that the total number of workouts was significantly associated with improved spatial navigation abilities and body image as well as reduced anxiety, general negative affect, fear, sadness, hostility, rumination, and disordered eating. In addition, increases in fitness levels were significantly associated with improved episodic memory and exercise motivation as well as decreased stress and disordered eating. Our findings are some of the first to indicate that in middle-aged moderately-fit adults, continuing to increase exercise levels in an already ongoing fitness regimen is associated with additional benefits for both psychological and cognitive health.
  • Assessing Human Spatial Navigation in a Virtual Space and its Sensitivity to Exercise
    Smith, Alana J.; Tasnim, Noor; Psaras, Zach; Gyamfi, Daphne; Makani, Krishna; Suzuki, Wendy A.; Basso, Julia C. (MyJove Corporation, 2024-01-26)
    Spatial navigation (SN) is the ability to locomote through the environment, which requires an understanding of where one is located in time and space. This capacity is known to rely on the sequential firing of place cells within the hippocampus. SN is an important behavior to investigate as this process deteriorates with age, especially in neurodegenerative disorders. However, the investigation of SN is limited by the lack of sophisticated behavioral techniques to assess this hippocampal-dependent task. Therefore, the goal of this protocol was to develop a novel, real-world approach to studying SN in humans. Specifically, an active virtual SN task was developed using a cross-platform game engine. During the encoding phase, participants navigated their way through a virtual city to locate landmarks. During the remembering phase, participants remembered where these reward locations were and delivered items to these locations. Time to find each location was captured and episodic memory was assessed by a free recall phase, including aspects of place, order, item, and association. Movement behavior (x, y, and z coordinates) was assessed through an asset available in the game engine. Importantly, results from this task demonstrate that it accurately captures both spatial learning and memory abilities as well as episodic memory. Further, findings indicate that this task is sensitive to exercise, which improves hippocampal functioning. Overall, the findings suggest a novel way to track human hippocampal functioning over the course of time, with this behavior being sensitive to physical activity training paradigms.
  • Effects of a Neuroscience-Based Mindfulness Meditation Program on Psychological Health: Pilot Randomized Controlled Trial
    Lynn, Sarah; Basso, Julia C. (JMIR Publications, 2023)
    Background: Mindfulness and meditation have a rich historical tradition, and a growing scientific base of evidence supports their use in creating positive psychological and neuroplastic changes for practitioners. Although meditation can be taught in various ways, the scientific community has yet to systematically study the impact of different types of meditation on neuropsychological outcomes, especially as it pertains to digital implementation. Therefore, it is critical that the instruction of mindfulness be evidence based because meditation is being used in both scientific and clinical settings. Objective: This study investigated the use of teacher cueing and the integration of neuroscience education into a meditation program. Compassion cueing was chosen as the element of experimental manipulation because traditional lineages of Buddhist meditation teach compassion for self and others as one of the primary outcomes of meditation. We hypothesized that participants receiving compassion cueing would have enhanced neuropsychological outcomes compared with those receiving functional cueing and that gains in neuroscience knowledge would relate to positive neuropsychological outcomes. Methods: Participants (n=89) were randomized to receive either functional cueing (control group) or compassion cueing (experimental group) and engaged with five 10-minute meditation sessions a week for 4 weeks. All intervention sessions were administered through digital presentation. All participants completed ecological momentary assessments before and after the daily intervention, as well as pre- and postintervention questionnaires. Results: Participants demonstrated significant benefits over time, including increased mindfulness and self-compassion, decreased depression, and gains in neuroscience content (all P<.001); however, no significant between-group differences were found. Daily scores from each day of the intervention showed a statistically significant shift from active toward settled. Importantly, long-term increases in mindfulness were positively correlated to changes in compassion (r=0.326; P=.009) and self-compassion (r=0.424; P<.001) and negatively correlated to changes in anxiety (r=–0.266; P=.03) and depression (r=–0.271; P=.03). Finally, the acute effects of meditation were significantly correlated to the longitudinal outcomes (with a small-to-medium effect size), especially those relevant to mindfulness. Conclusions: We developed a novel neuroscience-based education–meditation program that enhanced self-regulation as evidenced by improved mindfulness, self-compassion, and mood state. Our findings demonstrate the behavioral importance of engaging with mindfulness meditation and reinforce the idea that the benefits of meditation are independent of teacher cueing behavior. Future studies will need to investigate the brain-based changes underlying these meditation-induced outcomes.
  • Dispositional mindfulness and its relationship to exercise motivation and experience
    Lynn, Sarah; Satyal, Medha Kumari; Smith, Alana J.; Tasnim, Noor; Gyamfi, Daphne; English, Daniel F.; Suzuki, Wendy A.; Basso, Julia C. (Frontiers Media, 2022-11-29)
    Mindfulness is the psychological state of staying attuned to the present moment, without ruminating on past or future events, and allowing thoughts, feelings, or sensations to arise without judgment or attachment. Previous work has shown that heightened dispositional mindfulness is associated with the awareness of the importance of exercise, exercise self-efficacy, exercise motivation, and self-reported exercise level. However, more methodologically rigorous studies are needed to understand the relationship between mindfulness and the psychological mechanisms related to exercise motivation, including the identification of why individuals are motivated to engage in exercise, the subjective experience of exercise, and the propensity for exercise dependence and addiction. In this cross-sectional investigation, we utilized the framework of the Self-Determination Theory to examine the hypothesis that heightened dispositional mindfulness (as measured by the Mindful Attention Awareness Scale) would be associated with increased levels of exercise motivation that were derived by higher levels of autonomous self-regulation. Individuals were recruited from urban areas who self-reported either low (exercising 2 or fewer times per week for 20 min or less; n = 78) or moderate (exercising 1 or 2 times per week for 20 min or more; n = 127) levels of exercise engagement. As hypothesized, heightened dispositional mindfulness was significantly associated with heightened levels of exercise self-determination as measured by the Behavioral Regulations in Exercise Questionnaire, with this effect being driven by negative associations with amotivation, external regulation, and introjected regulation. Additionally, we found that heightened dispositional mindfulness was associated with lower levels of psychological distress upon exercise and decreased exercise dependence/addiction. Overall, increased dispositional mindfulness may support a healthy relationship with exercise. These findings have implications for the utility of mindfulness interventions to support the regulation of exercise behaviors in service of enhancing exercise motivation and engagement.
  • Development and validation of the multidimensional impacts of movement scale (MIMS) for yoga, weightlifting, and running
    Lynn, Sarah; Basso, Julia C. (Frontiers Media, 2023-03-01)
    Background: Movement is an essential element in maintaining overall well-being, producing both physical and mental health benefits. Yoga is a mindful movement practice, with traditional yogic texts providing a framework, called the Koshas, that delineates how an intentional movement practice may impact multidimensional aspects of an individual. To date, no self-report measure examines the multifaceted ways that movement affects the individual at a physical and psychological level. Therefore, we developed the Multidimensional Impacts of Movement Scale (MIMS) by aligning ancient yogic traditions with current neuroscientific concepts. Methods: MIMS was developed based on the five categories of the Koshas; 9 questions per Kosha resulted in 45 total questions. Participants (n = 103) selfidentified as having yoga, running, or weightlifting as their primary movement practice, engaging in this practice at least 30 min per session, once a week, for the past 3 months. Participants engaged in their usual movement practice and then (within 2 h of their workout session) completed the MIMS along with a series of previously validated questionnaires. After a period of 2 weeks, participants completed their normal movement practice once again and took the MIMS a second time to assess test–retest reliability and Cronbach’s alpha. Validity testing included convergent and divergent validity testing through Pearson’s productmoment correlations and confirmatory factor analysis. Results: One-hundred and three participants completed all study measures. Test– retest reliability demonstrated stability over time (r = 0.737, p < 0.001). Cronbach’s alpha was between 0.775 and 0.840 for each of the factors, p < 0.001. MIMS was sensitive to confirmatory and discriminatory validity testing. Validity was also demonstrated through confirmatory factor analysis (i.e., Chi Square, Comparative Fit Index, Root Mean Square Error of Approximation). Conclusion: MIMS is a valid and reliable tool to measure the multidimensional impacts of movement. The tool provides information about the effects of movement on a range of physical and psychological elements including subscales representing the body, energy, mind, intuition, and contentment. Physical activities that include aspects of mindfulness may demonstrate the most robust effects on the MIMS.
  • How does eligibility for GusNIP produce prescriptions relate to fruit and vegetable purchases and what factors shape the relationship? A protocol for a secondary analysis of nationally representative data in the USA
    Houghtaling, Bailey; Zhang, Nanhua; Yaroch, Amy; Atkinson, Clare Milburn; Shanks, Carmen Byker (BMJ, 2024)
    Introduction: US Department of Agriculture (USDA) Gus Schumacher Nutrition Incentive Programme (GusNIP) produce prescription programme (PPR) ‘prescriptions’ provide eligible participants with low income, risk for diet-related chronic disease and food insecurity a healthcare issued incentive to purchase lower to no cost fruits and vegetables (FVs). However, GusNIP requirements specify that PPR prescriptions can only be redeemed for fresh (not frozen, canned or dried) FVs. This requirement may prevent participants from fully engaging in or benefiting from GusNIP PPR, given communities with lower healthy food access may have reduced fresh FV accessibility. Methods and analysis: We will use the nationally representative 2012–2013 National Household Food Acquisition and Purchase Survey (FoodAPS) and complementary FoodAPS Geography Component data in a secondary data analysis to examine how household GusNIP PPR eligibility relates to the quantity and variety of fresh, frozen, canned and dried FV purchases and to what extent individual, household and food environment factors shape the relationship. FoodAPS data include household food purchasing and acquisition information across a 7 day period from 14 317 individuals among 4826 households and was collected between April 2012 and January 2013. The FoodAPS Geography Component provides information about the local community/environment relative to FoodAPS households. This study will examine the correlation or association of selected variables between different quantities and varieties of fresh, frozen, canned and dried FVs, as well as correlations among multilevel predictors. Ethics and dissemination: We are following data integrity standards as outlined by agreements with the USDA Economic Research Service. All results of analyses will undergo a thorough disclosure review to ensure no identifiable data are shared. Results will be disseminated to research, practice and policy communities using an Open Access peer-reviewed manuscript(s), scientific and practice presentations, and a public facing report and infographic.
  • Implementation of Food is Medicine Programs in Healthcare Settings: A Narrative Review
    Houghtaling, Bailey; Short, Eliza; Shanks, Carmen Byker; Stotz, Sarah A.; Yaroch, Amy; Seligman, Hilary; Marriott, James P.; Eastman, Jenna; Long, Christopher R. (Springer Nature, 2024-04-25)
    Food is Medicine (FIM) programs to improve the accessibility of fruits and vegetables (FVs) or other healthy foods among patients with low income and diet-related chronic diseases are promising to improve food and nutrition security in the United States (US). However, FIM programs are relatively new and implementation guidance for healthcare settings using an implementation science lens is lacking. We used a narrative review to describe the evidence base on barriers and facilitators to FIM program integration in US healthcare settings following the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework. Evidence surrounding the EPIS Inner Context was a focus, including constructs Leadership, Organizational Characteristics, Quality and Fidelity Monitoring and Support, Organizational Staffing Processes, and Individual Characteristics. Peer-reviewed and grey literature about barriers and facilitators to FIM programs were of interest, defined as programs that screen and refer eligible patients with dietrelated chronic disease experiencing food insecurity to healthy, unprepared foods. Thirty-one sources were included in the narrative review, including 22 peer-reviewed articles, four reports, four toolkits, and one thesis. Twenty-eight sources (90%) described EPIS Inner Context facilitators and 26 sources (84%) described FIM program barriers. The most common barriers and facilitators to FIM programs were regarding Quality and Fidelity Monitoring and Support (e.g., use of electronic medical records for tracking and evaluation, strategies to support implementation) and Organizational Staffing Processes (e.g., clear delineation of staff roles and capacity); although, barriers and facilitators to FIM programs were identified among all EPIS Inner Context constructs. We synthesized barriers and facilitators to create an EPIS-informed implementation checklist for healthcare settings for use among healthcare organizations/ providers, partner organizations, and technical assistance personnel. We discuss future directions to align FIM efforts with implementation science terminology and theories, models, and frameworks to improve the implementation evidence base and support FIM researchers and practitioners.
  • Exploring the Landscape of Media Campaigns That Encourage or Discourage Sustainable Diet Transitions for Americans, 1917–2023: A Systematic Scoping Review
    Consavage Stanley, Katherine; Leary, Nicole; Holz, Adrienne; Hedrick, Valisa E.; Serrano, Elena L.; Kraak, Vivica (MDPI, 2024-05-24)
    United States (U.S.) and global experts recommend that populations reduce red and processed meat (RPM) intake and transition to plant-rich, sustainable diets to support human and planetary health. A systematic scoping review was conducted to identify the landscape of media campaigns that promote plant-rich dietary patterns, traditional plant proteins, and novel plant-based meat alternatives (PBMA) and that encourage or discourage RPM products to Americans. Of 8321 records screened from four electronic databases, 103 records were included, along with 62 records from gray literature sources. Across 84 media campaigns (1917–2023) identified, corporate marketing campaigns (58.6%) were most prevalent compared to public information (13.8%), corporate sustainability (12.6%), countermarketing (5.7%), social marketing (4.6%), and public policy (4.6%) campaigns. Findings indicate that long-running corporate RPM campaigns, many with U.S. government oversight, dominated the landscape for decades, running alongside traditional plant protein campaigns. Novel PBMA campaigns emerged in the past decade. Many civil society campaigns promoted plant-rich dietary patterns, but few utilized social norm or behavior change theory, and only the Meatless Monday campaign was evaluated. The U.S. government, academia, businesses, and civil society should commit more resources to and evaluate the impact of media campaigns that support a sustainable diet transition for Americans, restrict and regulate the use of misinformation in media campaigns, and prioritize support for plant-based proteins and plant-rich dietary patterns.
  • Differing Within-Household Food Security Statuses Are Associated with Varied Maternal Mental Health Outcomes
    Liebe, Rachel A.; Holmes, Chanit’a; Misyak, Sarah A. (MDPI, 2024-05-18)
    Household food insecurity is not necessarily equally experienced by all household members, with mothers often changing their intake first when food resources are limited. The purpose of this study was to understand the association between maternal mental health and intrahousehold differences in food security statuses. A cross-sectional survey was administered to Virginia mothers with low income (August–October 2021), assessing validated measures of food security, mental and physical health and related factors. Participants (n = 570) were grouped according to the food security status of adults and children within the household. Linear regression was used to assess the outcomes of interest by group and controlled for key demographic variables. Mothers in households with any food insecurity reported worse overall mental health and used 3–4 more food coping strategies than households experiencing food security (p < 0.05). Only mothers in households where adults experienced food insecurity reported significantly greater anxiety and depressive symptoms (61.5 and 58.1, respectively) compared to households experiencing food security (55.7 and 52.4, p < 0.001). While any experience of household food insecurity is associated with worse maternal mental health, there were differences by the within-household food security status. Future research should explore screening measures that capture specific household members’ food security to connect households with available resources.
  • Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice
    Luo, Jing; Alkhalidy, Hana; Jia, Zhenquan; Liu, Dongmin (MDPI, 2024-03-29)
    Type 2 diabetes (T2D) is still a fast-growing health problem globally. It is evident that chronic insulin resistance (IR) and progressive loss of β-cell mass and function are key features of T2D etiology. Obesity is a leading pathogenic factor for developing IR. The aim of the present study was to determine whether sulforaphane (SFN), a natural compound derived from cruciferous vegetables, can prevent (prevention approach) or treat (treatment approach) obesity and IR in mouse models. We show that dietary intake of SFN (0.5 g/kg of HFD) for 20 weeks suppressed high-fat diet (HFD)-induced fat accumulation by 6.04% and improved insulin sensitivity by 23.66% in young male mice. Similarly, dietary provision of SFN (0.25 g/kg) significantly improved blood lipid profile, glucose tolerance, and insulin sensitivity of the middle-aged male mice while it had little effects on body composition as compared with the HFD group. In the treatment study, oral administration of SFN (40 mg/kg) induced weight loss and improved insulin sensitivity and plasma lipid profile in the diet-induced-obesity (DIO) male mice. In all three studies, the metabolic effects of SFN administration were not associated with changes in food intake. In vitro, SFN increased glucose uptake in C2C12 myotubes and increased fatty acid and pyruvate oxidation in primary human skeletal muscle cells. Our results suggest that SFN may be a naturally occurring insulin-sensitizing agent that is capable of improving the metabolic processes in HFD-induced obesity and IR and thereby may be a promising compound for T2D prevention.
  • A Scoping Review of Food Systems Governance Frameworks and Models to Develop a Typology for Social Change Movements to Transform Food Systems for People and Planetary Health
    Kraak, Vivica; Niewolny, Kimberly L. (MDPI, 2024-02-09)
    Effective governance is essential to transform food systems and achieve the United Nations (UN) Sustainable Development Goals 2030. Different political ideologies and paradigms inhibit or drive social change movements. This study examined how food systems governance has been described. Thereafter, we reviewed graphic frameworks and models to develop a typology for civil society actors to catalyze social change movements to transform food systems for people and the planet. The scoping review involved (1) formulating research questions; (2) developing a search strategy to identify evidence from four English-language electronic databases and reports, 2010–2023; and (3–4) selecting, analyzing, and synthesizing evidence into a narrative review. Results yielded 5715 records, and 36 sources were selected that described and depicted graphic frameworks and models examined for purpose, scale, political ideology, paradigm, discourse, principles, governance, and democracy. Evidence was used to develop a graphic food systems governance typology with distinct political ideologies (i.e., neoliberal, reformist, progressive, radical); paradigms (i.e., maintain, reform, transition, transform); discourses (i.e., food enterprise, food security, food justice, food sovereignty); types of governance (i.e., multistakeholder, shared, self); and democracy (i.e., representative, participatory, deliberative). This proof-of-concept typology could be applied to examine how change agents use advocacy and activism to strengthen governance for sustainable diets, regenerative food systems, and planetary health.
  • Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease
    Brisendine, Matthew H.; Nichenko, Anna S.; Bandara, Aloka B.; Willoughby, Orion S.; Amiri, Niloufar; Weingrad, Zach; Specht, Kalyn S.; Bond, Jacob M.; Addington, Adele; Jones III, Ronald G.; Murach, Kevin A.; Poelzing, Steven; Craige, Siobhan M.; Grange, Robert W.; Drake, Joshua C. (Oxford University Press, 2023-12-04)
    Alzheimer's disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur years earlier in those that develop AD; however, it is unknown what causes these peripheral phenotypes in a disease of the brain. Exercise promotes muscle, mitochondria, and cognitive health and is proposed to be a potential therapeutic for AD, but no study has investigated how skeletal muscle adapts to exercise training in an AD-like context. Utilizing 5xFAD mice, an AD model that develops ad-like pathology and cognitive impairments around 6 mo of age, we examined in vivo neuromuscular function and exercise adapations (mitochondrial respiration and RNA sequencing) before the manifestation of overt cognitive impairment. We found 5xFAD mice develop neuromuscular dysfunction beginning as early as 4 mo of age, characterized by impaired nerve-stimulated muscle torque production and compound nerve action potential of the sciatic nerve. Furthermore, skeletal muscle in 5xFAD mice had altered, sex-dependent, adaptive responses (mitochondrial respiration and gene expression) to exercise training in the absence of overt cognitive impairment. Changes in peripheral systems, specifically neural communication to skeletal muscle, may be harbingers for AD and have implications for lifestyle interventions, like exercise, in AD.
  • Prolonged voluntary wheel running reveals unique adaptations in mdx mice treated with microdystrophin constructs +/- the nNOS-binding site
    Hamm, S. E.; Yuan, C.; McQueen, L. F.; Wallace, M. A.; Zhang, H.; Arora, A.; Garafalo, A. M.; McMillan, R. P.; Lawlor, M. W.; Prom, M. J.; Ott, E. M.; Yan, J.; Addington, A. K.; Morris, C. A.; Gonzalez, J. P.; Grange, R. W. (Frontiers, 2023-06-26)
    We tested the effects of prolonged voluntary wheel running on the muscle function of mdx mice treated with one of two different microdystrophin constructs. At 7 weeks of age mdx mice were injected with a single dose of AAV9-CK8-microdystrophin with (gene therapy 1, GT1) or without (gene therapy 2, GT2) the nNOS-binding domain and were assigned to one of four gene therapy treated groups: mdxRGT1 (run, GT1), mdxGT1 (no run, GT1), or mdxRGT2 (run,GT2), mdxGT2 (no run, GT2). There were two mdx untreated groups injected with excipient: mdxR (run, no gene therapy) and mdx (no run, no gene therapy). A third no treatment group, Wildtype (WT) received no injection and did not run. mdxRGT1, mdxRGT2 and mdxR performed voluntary wheel running for 52 weeks; WT and remaining mdx groups were cage active. Robust expression of microdystrophin occurred in diaphragm, quadriceps, and heart muscles of all treated mice. Dystrophic muscle pathology was high in diaphragms of non-treated mdx and mdxR mice and improved in all treated groups. Endurance capacity was rescued by both voluntary wheel running and gene therapy alone, but their combination was most beneficial. All treated groups increased in vivo plantarflexor torque over both mdx and mdxR mice. mdx and mdxR mice displayed ∼3-fold lower diaphragm force and power compared to WT values. Treated groups demonstrated partial improvements in diaphragm force and power, with mdxRGT2 mice experiencing the greatest improvement at ∼60% of WT values. Evaluation of oxidative red quadriceps fibers revealed the greatest improvements in mitochondrial respiration in mdxRGT1 mice, reaching WT levels. Interestingly, mdxGT2 mice displayed diaphragm mitochondrial respiration values similar to WT but mdxRGT2 animals showed relative decreases compared to the no run group. Collectively, these data demonstrate that either microdystrophin construct combined with voluntary wheel running increased in vivo maximal muscle strength, power, and endurance. However, these data also highlighted important differences between the two microdystrophin constructs. GT1, with the nNOS-binding site, improved more markers of exercise-driven adaptations in metabolic enzyme activity of limb muscles, while GT2, without the nNOS-binding site, demonstrated greater protection of diaphragm strength after chronic voluntary endurance exercise but decreased mitochondrial respiration in the context of running.
  • Exerkines, Nutrition, and Systemic Metabolism
    Watkins, Bruce A.; Smith, Brenda J.; Volpe, Stella L.; Shen, Chwan-Li (MDPI, 2024-01-30)
    The cornerstones of good health are exercise, proper food, and sound nutrition. Physical exercise should be a lifelong routine, supported by proper food selections to satisfy nutrient requirements based on energy needs, energy management, and variety to achieve optimal metabolism and physiology. The human body is sustained by intermediary and systemic metabolism integrating the physiologic processes for cells, tissues, organs, and systems. Recently, interest in specific metabolites, growth factors, cytokines, and hormones called exerkines has emerged to explain cooperation between nutrient supply organs and the brain during exercise. Exerkines consist of different compounds described as signaling moiety released during and after exercise. Examples of exerkines include oxylipin 12, 13 diHOME, lipid hormone adiponectin, growth factor BDNF, metabolite lactate, reactive oxygen species (ROS), including products of fatty acid oxidation, and cytokines such as interleukin-6. At this point, it is believed that exerkines are immediate, fast, and long-lasting factors resulting from exercise to support body energy needs with an emphasis on the brain. Although exerkines that are directly a product of macronutrient metabolism such as lactate, and result from catabolism is not surprising. Furthermore, other metabolites of macronutrient metabolism seem to be candidate exerkines. The exerkines originate from muscle, adipose, and liver and support brain metabolism, energy, and physiology. The purpose of this review is to integrate the actions of exerkines with respect to metabolism that occurs during exercise and propose other participating factors of exercise and brain physiology. The role of diet and macronutrients that influence metabolism and, consequently, the impact of exercise will be discussed. This review will also describe the evidence for PUFA, their metabolic and physiologic derivatives endocannabinoids, and oxylipins that validate them being exerkines. The intent is to present additional insights to better understand exerkines with respect to systemic metabolism.
  • Impacting Community Well-Being Through Effective Engagement Using the Stakeholder Engagement in Research Question Development Method
    Rafie, Carlin; Zimmerman, Emily; Hargrove, Angelina; Biney-Amissay, Theodora; Lee, Samantha (2024)
  • Hedgehog-interacting protein acts in the habenula to regulate nicotine intake
    Caligiuri, Stephanie P. B.; Howe, William M.; Wills, Lauren; Smith, Alexander C. W.; Lei, Ye; Bali, Purva; Heyer, Mary P.; Moen, Janna K.; Ables, Jessica L.; Elayouby, Karim S.; Williams, Maya; Fillinger, Clementine; Oketokoun, Zainab; Lehmann, Vanessa E.; DiFeliceantonio, Alexandra G.; Johnson, Paul M.; Beaumont, Kristin; Sebra, Robert P.; Ibanez-Tallon, Ines; Kenny, Paul J. (National Academy of Sciences, 2022-11-08)
    Hedgehog-interacting protein (HHIP) sequesters Hedgehog ligands to repress Smoothened (SMO)-mediated recruitment of the GLI family of transcription factors. Allelic variation in HHIP confers risk of chronic obstructive pulmonary disease and other smoking-related lung diseases, but underlying mechanisms are unclear. Using single-cell and cell-type-specific translational profiling, we show that HHIP expression is highly enriched in medial habenula (MHb) neurons, particularly MHb cholinergic neurons that regulate aversive behavioral responses to nicotine. HHIP deficiency dysregulated the expression of genes involved in cholinergic signaling in the MHb and disrupted the function of nicotinic acetylcholine receptors (nAChRs) through a PTCH-1/cholesterol-dependent mechanism. Further, CRISPR/Cas9-mediated genomic cleavage of the Hhip gene in MHb neurons enhanced the motivational properties of nicotine in mice. These findings suggest that HHIP influences vulnerability to smoking-related lung diseases in part by regulating the actions of nicotine on habenular aversion circuits.
  • Cardiovascular aging: from cellular and molecular changes to therapeutic interventions
    Vakka, Angeliki; Warren, Junco S.; Drosatos, Konstantinos (OAE Publishing, 2023-07-01)
    Progressive age-induced deterioration in the structure and function of the cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction. These changes are driven by complex processes that are interconnected, such as oxidative stress, mitochondrial dysfunction, autophagy, inflammation, fibrosis, and telomere dysfunction. In recent years, the advances in research of cardiovascular aging, including the wide use of animal models of cardiovascular aging, elucidated an abundance of cell signaling pathways involved in these processes and brought into sight possible interventions, which span from pharmacological agents, such as metformin, sodium-glucose cotransporter 2-inhibitors, rapamycin, dasatinib and quercetin, to lifestyle changes.