Digital Commons Network^™

Current And Emerging Therapeutic Strategies For The Treatment Of Duchenne Muscular Dystrophy, Miguel A. Lopez Perez, Noah L. Weisleder

Molecular and Cellular Biochemistry Faculty Publications

Background/Objectives: Duchenne muscular dystrophy (DMD) is a fatal, progressive neuromuscular disorder caused by mutations in the dystrophin gene, leading to the absence of functional dystrophin protein. As the largest gene in the human genome, the DMD locus is highly susceptible to mutations, contributing to a prevalence of approximately 1 in 3800–6300 live male births worldwide. This review aims to provide a comprehensive and critical synthesis of current and emerging therapeutic strategies for DMD.

Methods: We conducted a narrative review of the literature, integrating findings from clinical trials, regulatory approvals, and preclinical studies. We categorized therapeutic approaches into mutation-agnostic and mutation-specific …

Adipose Tissue-Derived Small Extracellular Vesicles In Plasma Reveal Molecular Circuitries Underlying Glucose Intolerance, Shalini Mishra, Yixin Su, Ashish Kumar, Sangeeta Singh, Brian S. Finlin, Fang-Chi Hsu, Jingyun Lee, Cristina M. Furdui, Philip A. Kern, Swapan K. Das, Gagan Deep

Internal Medicine Faculty Publications

Objective: Glucose tolerance (GT) is a major effector for adipose tissue (AT) remodeling in obesity, yet its molecular mechanisms remain incompletely defined. We hypothesized that the biophysical and molecular profiles of AT-derived small extracellular vesicles (sEV^AT) change in response to glucose availability and differ by GT status.

Methods: sEV^AT were isolated from plasma of individuals with normal GT (NGT) and impaired GT (IGT) (n = 5/group) at fasting (0 h) and 1 h post glucose challenge during oral glucose tolerance test (OGTT). sEV^AT were characterized for size, concentration, surface expression of insulin receptor-α (INSRα), proteome, …

Childhood Mental Health And Major Depression In Later Life: A Survival Analysis Across 12 Years, Xiaoling Xiang, Xiafei Wang, Xinyin Zhang, Josephine Abrials

Social Work Faculty Publications

Objectives: This study examined the relationship between childhood mental health conditions and incident major depression in middle-aged and older adults.

Methods: This longitudinal panel study used 12 years of data from 27,220 adults aged 51 and older in the U.S. Health and Retirement Study. Childhood mental health conditions were assessed retrospectively with a question about having a depression, drug/alcohol, or other emotional problem before age 16. Cox regression was used to estimate hazard ratios (HRs).

Results: Childhood mental health conditions were reported by 6.04% of the unweighted sample (n = 1643) and were associated with a more than 2-fold …

Cultus: Eco-Phenomenology In The Work Of John Steinbeck, Robinson Jeffers, And Jack London, Carter D. Johnson

Theses and Dissertations--English

In the face of increasingly dire environmental crises, proposed solutions have gravitated toward imperatives for faster, cleaner, and more efficient technologies and resources. While practical solutions are necessary, they are entirely insufficient to deal with an underlying issue driving environmental degradation: unbridled instrumental reason. In this dissertation, I suggest a theoretical posture, cultus, which attempts to balance the necessity of instrumental action with the guiding counterweight of receptivity. Furthermore, I argue that such personal receptivity is uniquely fostered in aesthetic experiences, attuning the individual to the non-identical and renewing a relationship of care.

I examine the life and work of …

Advancing Generative Methods For Multimodal Data Analysis, Rabeya Tus Sadia

Theses and Dissertations--Computer Science

The integration and modeling of high-dimensional, heterogeneous biological data remain central challenges in computational biology due to complex feature dependencies and pervasive missingness. This dissertation addresses these challenges by developing novel generative frameworks for multimodal data reconstruction, imputation, and interaction prediction. In generative modeling, we focus on capturing structural and causal dependencies in sparse biological systems. We first introduce CausalGeD, a causality-aware diffusion framework that leverages Granger-causal attention for biologically coherent spatial gene expression generation. Next, we propose CausalGenDiff, which combines VAE-guided latent representations with causal diffusion to enable robust reconstruction across spatial and single-cell modalities. We further present DepMicroDiff, …

Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone …

Affordability And Serving Accuracy Of A Publicly Available Dash Meal Plan For Women Using Snap Benefits, Kendra Oonorasak, Mansura Shahad Bawa, Nadia Ayesha Sesay, Emma Smith, Taylor Emerson, Jayden Brewer, Brandi M. White

Health and Clinical Sciences Faculty Publications

Background/Objectives: This regional case study evaluated the affordability and serving accuracy of a publicly available one-week DASH meal plan for single-woman households using Supplemental Nutrition Assistance Program (SNAP) benefits in central Kentucky.

Methods: For each food item in the one-week plan, total grocery costs and per-serving costs were calculated using January 2025 prices from two national grocery chains commonly patronized in an urban area in central Kentucky. Calculated costs were compared to the average weekly food cost for women aged 20–50 years in a single household based on the Thrifty Food Plan (TFP). Servings for food groups and categories were …

Abca12 Frameshift Deletion In Domestic Cats With Ichthyosis Fetalis, Jeanna M. Blake, Melissa P. Swan, Kari J. Ekenstedt

Veterinary Science Faculty Publications

Background: Ichthyosis fetalis (IF), also known as harlequin ichthyosis, is a rare and often fatal autosomal recessive congenital skin disorder. It is characterized by thickened, hard skin plaques and deep skin fissures that limit mobility and cause malformations of the eyes, lips and ears. Affected individuals are highly susceptible to life-threatening infections due to the disruption of the skin's protective barrier. To date, IF and its genetic basis have not been described in domestic cats.

Objectives: To characterize the gross clinical, histopathological and genetic features of IF in two stray, random-bred domestic short-hair (DSH) littermates.

Animals: Two deceased female neonatal …

Different Destinations: Clarifying And Addressing Pipeline Problems For Women In Academic Archaeology, Scott R. Hutson, Jaycee Castro, Bruno Athie Teruel

Anthropology Faculty Publications

In STEM fields, women tend to leak out of the pipeline to the professoriate. In archaeology, however, robust databases and chronological control reveal that there is no leakage from earning a PhD to tenure-track positions. Nor is there a leak from assistant professor to associate professor. Nevertheless, men get hired as faculty in PhD programs more often than women. This is important because PhD programs are research-intensive and train future leaders. Furthermore, women PhD students have women as advisers more than often men and report advantages to this arrangement. Yet with fewer women faculty in PhD programs, women mentors are …

Complex Interplay Between Facilitation And Competition In Two Invasive Fruit Pests, Eleanor Mccabe, Nicholas M. Teets

Entomology Faculty Publications

When one invasive species facilitates the invasion of another species, it can lead to invasional meltdown. However, when the two species depend on the same finite resource, facilitation and competition can occur simultaneously and impact population dynamics. Furthermore, factors like resource availability and population density could alter the balance between facilitation and competition. Drosophila suzukii and Zaprionus indianus are two invasive insect pests that infest small fruit crops. The co-localization of these species in the same fields, coupled with the fact that Z. indianus lacks a hardened ovipositor that can penetrate the skin of fruit, has led to the hypothesis …

Elevated Temperatures Disrupt Wolbachia-Induced Feminisation And Reshape Microbial Community Dynamics Across Generations In A Spider Host, Virginija Mackevicius-Dubickaja, Jennifer A. White, Ellen E. Williams, Eyal Klement, Yuval Gottlieb, Matthew R. Doremus

Entomology Faculty Publications

Longitudinal microbial interactions within a host are challenging to study, leading to a focus on constructed microbial communities in vitro settings. Here, we take advantage of a naturally defined microbial community within a spider host to study how elevated temperatures influence microbial dynamics and phenotypes across host generations. The spider Mermessus fradeorum hosts up to five endosymbionts, including a Wolbachia strain, W1, which induces feminisation, causing genetic males to develop as phenotypic females, skewing sex ratios and promoting symbiont spread. Despite this, Wolbachia 1 persists at intermediate frequencies in wild populations. We hypothesised that elevated temperatures might reduce penetration of …

Evolutionary Transitions In Social Behavior Are Associated With Convergent And Partially Reversible Expansions Of Transcription Factor Binding Sites, Savanna G. Ploessl, Beryl M. Jones

Entomology Faculty Publications

The evolution of sociality involves shifts in physiology and behavior, most notably the emergence of a reproductive division of labor. Within social colonies, these distinct behavioral phenotypes arise from differential regulation of a shared genome. Changes in transcription factor (TF) binding motifs are one potential mechanism underpinning this plasticity, with prior studies suggesting that social species exhibit expansions in TF binding sites. However, it remains unclear whether motif expansions are reversed when sociality is lost. Here we analyze predicted TF motif occurrences across gene promoters in 42 bee species spanning millions of years of evolutionary divergence and multiple independent gains …

Variability In Mountain Pine Beetle (Coleoptera: Curculionidae) Gene Expression In Response To Increasing Concentrations Of Species-Specific Double-Stranded Rna, Kylie J. Bickler, Zachary Bragg, Flávia Pampolini, Bethany R. Kyre, Lynne K. Rieske

Entomology Faculty Publications

Sensitivity to double-stranded RNA (dsRNA)-induced gene silencing has been observed in multiple coleopterans. Initial work with mountain pine beetle, Dendroctonus ponderosae Hopkins, determined that specific ubiquitously expressed essential genes can cause mortality when silenced by carefully designed dsRNAs. However, current dsRNA production methods are not economically feasible for production at scale. Therefore, identifying the minimum efficacious dose is a critical step to deployment. To investigate the relationship between dsRNA dose and subsequent gene expression, adult mountain pine beetles were fed either a target or control dsRNA across a gradient of concentrations, including 2.5, 1.0, 0.25, and 0.025µg/µl, and relative gene …

Anuran Occupancy Of Created Wetlands Within Reforested Legacy Surface Mines In Kentucky And West Virginia, Jillian C. Newman, Steve Price, Jacquelyn C. Guzy, Joshua Castle, John J. Cox, Jeffery L. Larkin, Christopher D. Barton

Forestry and Natural Resources Faculty Publications

Restoration of habitat is an important component of wildlife management. Surface coal mining has altered forest cover in the Central Appalachians, and most reclamation activities on previously mined lands result in non-native grasslands or shrub lands. The Forestry Reclamation Approach (FRA), which emphasizes non-native vegetation removal, soil decompaction, planting of native trees and shrubs, and, in some cases, wetland creation represents an alternative to grassland-based reclamation that may promote forest-associated wildlife on legacy surface mines. We used automated recording units to evaluate the response of anurans to created wetlands and the FRA in Kentucky and West Virginia, USA. We used …

Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt

Theses and Dissertations--Physiology

APOE exists as three common alleles (APOE2, APOE3, APOE4) that encode their corresponding protein isoforms (apoE2, apoE3, apoE4). Despite differing by only one or two single-amino acid substitutions, each APOE allele confers a distinct AD risk profile with APOE4 increasing risk by 28% and APOE2 decreasing risk by 14% compared to the most commonly expressed APOE3 allele. While traditionally considered “neutral,” APOE3 still accounts for ~36% of AD cases while APOE4 contributes ~57%, indicating that the majority of AD cases would not occur in the absence of the APOE3 and APOE4 alleles. Microglia, the resident phagocytic immune cells …

Field-Scale Evaluation Of Satellite- Derived Vegetation Indices And Image Timing For In-Season Nitrogen Management In Corn, Ana Morales-Ona, Katsutoshi Mizuta, James J. Camberato, Robert Nielsen, Yuxin Miao, Davide Cammarano, German Mandrini, Daniel Quinn

Plant and Soil Sciences Faculty Publications

Introduction: Traditional methods to determine the agronomic optimum nitrogen rate (AONR) for corn (Zea mays L.) rely on grain yield data, limiting in-season decision-making for nitrogen (N) management. Vegetation indices (VIs) derived from satellite imagery can serve as proxies for grain yield and help estimate in-season AONR, enabling timely sidedress applications. This study aimed to (1) quantify how VI–yield relationships vary during the vegetative period across fields with different tillage systems and crop residue; (2) determine whether VI–N response curves can be used to estimate AONR (AONRvi); and (3) assess the accuracy of AONRvi relative to yield-based AONR (AONRy). …

Resilience Shields And Grit Intensifies Subjective Cognitive Decline In Middle‐To‐Older Aged Black Americans, Sunkanmi Folorunsho, Maria Clark, Obinna Odo, Yolanda L. Jackson, Candidus C. Nwakasi, Darlingtina K. Esiaka

Behavioral Science Faculty Publications

Background: There is growing interest on the relationship between psychosocial factors and cognitive health trajectories in adulthood. While grit and resilience have been shown to influence health outcomes, their differential effects on subjective cognitive decline (SCD) in Black American adults remain understudied. The purpose of this study is to help fill this gap.

Methods: The study utilized a cross-sectional research design. Black American participants (N = 242; Mean age = 44.32) responded to a survey assessing SCD, grit, resilience, and sociodemographic factors. Linear regression analysis was performed to test the associations between grit and resilience and SCD, and to …

Fiber-Reinforced Composites For Vaginal Tissue Engineering Applications, Samyuktha S. Kolluru, Abir Hamdaoui, Annabella M. Mascot, Siobhan S. Sutcliffe, Jerry L. Lowder, Michelle L. Oyen, Samantha G. Zambuto

Mechanical Engineering Faculty Publications

The vagina is a fibromuscular tube-shaped organ that plays critical roles in menstruation, pregnancy, and female sexual health. Vaginal tissue constituents, including cells and extracellular matrix components, contribute to tissue structure, function, and prevention of injury and pathology. However, much microstructural function remains unknown, including how the fiber-cell and cell–cell interactions influence macromechanical properties. A deeper understanding of these interactions will provide critical information needed to reduce and prevent vaginal pathologies. Our objective for this work is to design a novel tissue-mimicking biomaterial for vaginal tissue engineering, and characterize its biological and mechanical performance in the vaginal microenvironment. We successfully …

Emergency Department-Initiated Standard Versus High-Dose Buprenorphine Induction (Envision): A Randomised Clinical Trial Protocol, Kathryn Hawk, Andrew Herring, Marek Chawarski, Erik S. Anderson, Michael Baumann, Alyrene Dorey, August F. Holtyn, Christopher Jones, Shara Martel, Patricia Owens, Kaitlin Kmiecik, Tania D. Strout, Peter Taillac, Michelle R. Lofwall, Sharon L. Walsh, Gail D’Onofrio

Center on Drug and Alcohol Research Faculty Publications

Introduction: The initiation of buprenorphine for patients with opioid use disorder (OUD) in the emergency department (ED) has been associated with improved outcomes including reduced ED visits and increased treatment engagement. Though both standard-dose (8 mg buprenorphine equivalent) and high-dose (24 mg buprenorphine equivalent) strategies to initiate buprenorphine have been used in the ED, no prospective trials comparing outcomes among patients receiving these treatments have been reported.

Methods and analysis: This multisite randomised clinical trial is a multisite double-blind, double-dummy, randomised clinical trial enrolling 360 emergency department patients with moderate-to-severe OUD. Enrolled patients will be randomised to one of two …

Evolution Of A Client‐Level Dataset: 20 Years Of National Child Traumatic Stress Network Data Collection, C. A. Purbeck, A. N. Cooke, L. J. Liang, C. Smith, J. Staten, J. Epstein, H. B. Hodgdon, Jessica Eslinger, A. Wells, J. Goodrich, T. H. Bethel, K. Willett, Y. C. Fu, J. A. Fairbank, E. C. Briggs

Center on Trauma and Children Faculty Publications

Objectives: For 20 years, the National Child Traumatic Stress Network's (NCTSN) data collection efforts have been a central mechanism for Clinical Quality Improvement (ClQI). The NCTSN is a federally funded initiative in the United States composed of programs dedicated to raising the standard of care and increasing access to services for children and families who have experienced traumatic events.

Methods: These efforts span three initiatives: the Core Data Set (CDS), the Clinical Improvement through Measurement Initiative (CIMI) Measurement Based Care (MBC), and CIMI Data Sharing (CIMI-DS) that collected and analyzed client-level data to improve care for children and families served …

Music-Based Storytelling For Older Adult Well-Being: An Adapted Multiple Case Study, Zachary Michael Palma

Theses and Dissertations--Music

Autobiographical storytelling can be a meaningful way for older adults to reflect on life experience and support social and emotional well-being. Music has been widely documented as a cue for autobiographical memory. Although the benefits of storytelling and music as a memory cue have been independently examined, limited research has explored its combination with older adults. The purpose of this study was to explore music-based autobiographical storytelling in the lives of older adults. There were three research questions: (1) How do older adults describe their experiences with music-based storytelling? (2) How do they describe the social experience with music-based storytelling? …

Burnout And Mindful Self-Care Practices Among Bipoc Women Music Therapists: A Cross-Sectional Survey, Melissa V. Peters

Theses and Dissertations--Music

Music therapy as a profession has long acknowledged burnout as a significant occupational concern, yet the experiences of marginalized therapists remain understudied. In particular, little research has explored how burnout and self-care manifest for those who identify as Black, Indigenous, or People of Color (BIPOC) women in a field historically dominated by white women. Most of the existing literature on this topic is focused on the majority identity of music therapists, white women. The purpose of this thesis was to examine the reported levels of burnout among BIPOC women music therapists as well as their reported frequency of engagement in …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …

Excess Nitric Oxide Alters Cellular Ph To Restrict Salicylic Acid Movement And Systemic Immunity, Fan Xia, Huazhen Liu, Keshun Yu, Xinyu Yuan, Aardra Kachroo, Pradeep Kachroo

Plant Pathology Faculty Publications

Plants carrying a mutation in S-nitrosoglutathione reductase 1 (GSNOR1) accumulate high nitric oxide (NO) and exhibit impaired immunity characterized by reduced pathogen-responsive salicylic acid (SA) accumulation and failure to activate normal SA signaling. We show that this reduced SA responsiveness in gsnor1 plants arises from impaired vascular-associated movement of SA, thereby compromising systemic acquired resistance (SAR). Elevated NO perturbs cellular pH homeostasis, acidifying the apoplast and alkalinizing the cytosol, which likely interferes with phloem-associated SA movement and renders gsnor1 plants unresponsive to foliar SA. In contrast, SA supplied via root drench restores SA signaling and SAR in gsnor1, …

Dim Light At Night Impacts Circadian Rhythms And Alzheimer’S Disease-Like Neuroinf Lammation And Neuropathology In Humanized App Saa Knock-In Mice, Marilyn J. Duncan, Margaret R. Hawkins, Leke Bytyqi, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Esther G. Drinkard, Teresa Macheda, Kelly N. Roberts, Katharina Kohler, Mary-Claire Schmidt, Carrie E. Johnson, Sridhar Sunderam, Bruce F. O'Hara, Michael Paul Murphy, Adam D. Bachstetter

Neuroscience Faculty Publications

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing …

Endocranial Morphological Affinities Of The Early Holocene Individuals From Lagoa Santa And Implications For The Peopling Of The Americas, María Clara López-Sosa, Hugo Reyes-Centeno, Lumila Paula Menéndez, Rodrigo Elias Oliveira, Claudio Campi De Castro, André Strauss

Anthropology Faculty Publications

The ectocranial morphology of early Holocene humans from Lagoa Santa, Brazil has been described as exhibiting a ‘Paleoamerican’ form with affinities to African and Australasian individuals, in contrast to past and present Native Americans, who predominantly exhibit ‘Amerindian’ form. While this interpretation remains disputed, its led to the ‘Two Main Biological Components Model’, which proposes separate dispersals from Asia into the Americas. This study aims to assess whether the endocranial morphology of Lagoa Santa individuals similarly reflects these affinities. For this study, the overall endocranial morphology, as well as the temporal bones of the crania of twenty individuals from Lagoa …

Charge‐Governed Mechanistic Evaluation Of Aav2 Clarification Via Functionalized Flat Sheet And Hollow Fiber Deconstructed Depth Filters, Mara Baughman‐Leach, Mattie Brock, Malgorzata Chwatko, Dibakar Bhattacharyya

Chemical and Materials Engineering Faculty Publications

The expansion of adeno-associated virus (AAV)-based therapeutics has increased the demand for efficient clarification. In this study, a functionalized deconstructed depth filtration platform was developed to dissect how membrane–virus charge, modulated by pH, influences separation. Three charge regimes, positive (pH 4), neutral (pH 6), and negative (pH 8) between the membranes and AAVs, were examined. The flat-sheet system, composed of sequential 1.2, 0.8, 0.45, and 0.1 µm membranes, enabled the first layer-by-layer analysis of depth filtration behavior. This revealed that Stage 1 and Stage 4 dominate clarification. Remarkably, substantial DNA capture (> 75%) was observed even in the largest-pore stage, …

Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of …

Traumatic Brain Injury Exacerbates Mitochondrial Dysfunction In App/Ps1 Knock-In Mice Through Time-Dependent Pathways, Elika Z. Moallem, Hemendra J. Vekaria, Teresa Macheda, Margaret R. Hawkins, Kelly N. Roberts, Samir P. Patel, Patrick G. Sullivan, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cerebral hypometabolism occurs in both traumatic brain injury (TBI) and Alzheimer's disease (AD), but whether these conditions act through distinct or overlapping mechanisms is unclear. TBI disrupts cerebral metabolism via blood–brain barrier damage, altered glucose transporter expression, calcium buffering abnormalities, and oxidative damage to metabolic enzymes. AD-related hypometabolism is linked to amyloid-β (Aβ) effects on mitochondria, including impaired respiration, oxidative stress, and altered mitophagy, fusion, and fission. We tested whether TBI-induced mitochondrial dysfunction exacerbates Aβ-mediated impairment using a closed-head injury (CHI) model in APP/PS1 knock-in (KI) mice. Injuries were delivered at 4–5 months of age, before plaque formation and mitochondrial …