Digital Commons Network^™

Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …

Aluminum In Beverages And Foods: A Comprehensive Compilation Of Regulations; Concentrations In Raw, Prepared, And Stored Beverages And Foods; And Intake, Robert Yokel

Pharmaceutical Sciences Faculty Publications

The history and controversy concerning aluminum use in beverage and food preparation and storage are reviewed. This review on aluminum in drinking water, foods, and beverages updates and exceeds prior reviews. Country and international organization regulations that permit incorporation of aluminum containing food additives, their use limit, and purposes are presented. The aluminum concentration in beverages and foods consumed worldwide was gleaned from approximately 2100 sources available to the author. The approximately 17700 values are compiled in 175 tables by beverage or food category that include the analytical method used, sample source, and reference. The tables are posted on the …

Development Of A Ghrelin Deacylase To Attenuate Drug Reward And Associated Effects Of Methamphetamine, Madeline J. Stewart, Huimei Wei, Nellore Bhanu Chandar, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

All addictive substances directly or indirectly interact with the dopamine reward system to alter the brain’s dopamine receptor activities. It is essential for a truly effective addiction medication to attenuate substance reward and normalize the brain’s physiological functions. Conventional pharmacological intervention approaches to the treatment of substance addiction usually aim to develop and deliver a potential therapeutic agent to the brain to directly block or decrease actions of the substance or its therapeutic target in the brain. However, it is a grand challenge to attenuate the substance reward without affecting the normal physiological functions of brain receptors or transporters. Here, …

Effects Of Biased Analogues Of The Kappa Opioid Receptor Agonist, U50,488, In Preclinical Models Of Pain And Side Effects, Ross Van De Wetering, Loan Y. Vu, Lindsay D. Kornberger, Dan Luo, Brittany Scouller, Sheein Hong, Kelly F. Paton, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

Kappa opioid receptor (KOR) agonists have well-established antinociceptive effects. However, many KOR agonists have negative side effects, which limit their therapeutic potential. Some researchers have suggested that the development of biased agonists that preferentially stimulate KOR G-protein pathways over β-arrestin pathways may yield drugs with fewer adverse side effects. This was investigated in the current study. We describe the synthesis and characterization of three U50,488 analogues, 1, 2, and 3. We evaluated the acute and chronic antinociceptive effects of these compounds in mice using the warm-water tail flick assay and in a paclitaxel-induced neuropathic pain model. Side …

Effects Of Fentanyl-Adulterated Methamphetamine On Circulating Ghrelin In Rats, Huimei Wei, Elise C. Maul, Shawn Park, Kaniz Fatema, Daniel J. Peter, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl …

Effects Of Fentanyl-Laced Cocaine On Circulating Ghrelin, Insulin, And Glucose Levels In Rats, Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant …

Fluorescence-Guided Resection Of Gl261 Red-Fluc And Trp-Mcherry-Fluc Mouse Glioblastoma Tumors, Louis T. Rodgers, Bryan J. Maloney, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Background: Most preclinical studies on glioblastoma (GBM) fail to provide translational utility in the clinic. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) improves tumor resection, disease prognosis, and, thus, patient outcomes. Given the critical role of surgery in managing recurrent GBM, it is essential to incorporate surgical elements into preclinical models to accurately reflect clinical scenarios and enhance translational success. However, existing protocols for 5-ALA-guided resection in preclinical models are limited and often lack clinical relevance.

Methods: To address this gap, we developed a novel protocol for the 5-ALA-guided resection in two mouse GBM models: TRP-mCherry-FLuc and GL261 Red-FLuc.

Results: The …

Development Of Zafirlukast Analogues For Improved Antithrombotic Activity Through Thiol Isomerase Inhibition, Justine A. Keovilay, Kaitlind C. Howard, Kirk A. Taylor, Sabeeya Khan, Sienna E. Wurl, Melanie K. Szahaj, Tanya Sage, Nishad Thamban Chandrika, Caixia Hou, Oleg V. Tsodikov, Jonathan M. Gibbins, Sylvie Garneau-Tsodikova, Daniel R. Kennedy

Pharmaceutical Sciences Faculty Publications

Background:   Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.   Methods:   Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet …

Development Of A Stable Isotope Method To Measure Protein Fractional Synthesis Rate In Equine Skeletal Muscle, Antoinette E. Foliart

Theses and Dissertations--Animal and Food Sciences

Muscle mass is regulated by the balance between muscle protein synthesis and degradation. Previous research in horses has shown that the signaling pathway that regulates protein synthesis is upregulated with increasing protein intake; however, whether this corresponds to an increase in muscle protein synthesis rates had not been previously explored. The objective of this study was to develop an isotopic method to measure muscle protein fractional synthesis rate (FSR) in horses following graded protein intake. Eight mature Thoroughbred horses were studied using a randomized cross-over design. Horses consumed meals containing 0 (No), 0.125 (Low), 0.25 (Med), or 0.5 (High) g …

Examining The Relationship Between Cognitive Auditory Processing And Sex Hormones, Trey A. Cline

Theses and Dissertations--Gerontology

Estrogen and progesterone have demonstrated modulatory effects on central auditory nervous system (CANS) function. Post-menopausal females often present to audiology clinics with complaints of difficulty hearing in background noise. However, these individuals often have normal peripheral hearing sensitivity on standard audiometry. Previous studies using the auditory brainstem response (ABR) in post-menopausal females demonstrated longer response latencies compared to their premenopausal counterparts, suggesting that sound does not transmit through the CANS as efficiently. However, to date, the available literature focused on sex hormones and the CANS relies mainly on objective measures, predominantly the ABR. The ABR reflects physiologic function through the …

The Paradox Of Survival: Gendered Food Insecurity, Labor Inequalities, And Coping Strategies During The 2023/4 Drought In Eastern Ethiopia, Meron E. Lemma

Theses and Dissertations--Geography

In drought-prone regions of Eastern Ethiopia, recurring droughts profoundly reshape everyday life in ways that deepen existing gendered inequalities. Drawing on fieldwork conducted in Fedis district, including semi-structured interviews with women, project implementers, and government officials, as well as group discussions with community members, this study explores how women experience, navigate, and resist the gendered impacts of drought. By attending to the sociopolitical dynamics of drought and the development interventions that accompany it, I analyze how these forces restructure labor, land, food systems, and authority in ways that reproduce and exacerbate existing inequalities. Women’s coping strategies, ranging from begging and …

Igc Oral Presentation Summary: Xxv Igc Congress, S. Ray Smith, Echo Elizabeth Gotsick, J. R. Weinert-Nelson, Alayna Jacobs, Christopher D. Teutsch, Will Fleming, D. R. Woodfield, James L. Klotz, Jeff Lehmkuhler, Greg S. Halich, Brittany Davis, Brittany Hendrix, Krista Lea

IGC Proceedings (1977-2023)

This paper will give an overview of the XXV International Grassland Congress thematic, keynote, and plenary sessions. The theme of the XXV IGC Congress meeting was “Grasslands for Soil, Animal, and Human Health.” We had many people attending, presenting, and participating in all these sessions. Within a month after the conclusion of the Congress, the proceeding’s papers presented at the meeting will be available on the IGC app. By the end of 2023 all papers will be available for download through any search engine at internationalgrasslands.org.

“Single Girl, Married Girl:” Female Perspectives On Marriage, Maidenhood, And Motherhood In English-Language Folk Music, Avery Schanbacher

Libraries Award for Undergraduate Scholarship

In 1928, the Carter Family released “Single Girl, Married Girl.” The recording featured only Sara and Maybelle Carter, and in three short stanzas, highlighted the vastly differing lives of the single girl, who dressed fine and went where she pleased, and the married girl, with a baby on her knee, who rocked the cradle and cried. Sara and Maybelle Carter weren’t the only people who knew this song – before they recorded it for Ralph Peer at the famous Bristol sessions, it was alive as a part of musical traditions not just in their home in Scott County, Virginia, but …

A Case Study In Program Evaluation: Evaluation Of A Program Designed To Increase Activity Levels In Bourbon County Residents, Brooke M. Woodburn

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This paper provides recommendations to eliminate possible barriers in a program developed to reduce inactive levels across Bourbon County.

The Role Of Self-Efficacy In Rehabilitation And Recovery From Ankle Sprains, Bridget M. Walsh

Theses and Dissertations--Rehabilitation Sciences

Ankle sprains are among the most common musculoskeletal injuries in the United States. Approximately 2 million ankle sprains occur annually, with an estimated 46% of affected individuals experiencing residual symptoms and developing chronic ankle instability (CAI). In addition to physical impairments, individuals with CAI may exhibit lower physical and psychological health-related quality of life (HRQL). HRQL integrates the physical, psychological, and social domains of a person’s health and is influenced by their experiences, expectations, and perceptions.

Injury-related fear is a common psychological impairment in individuals with CAI and has been associated with decreased physical function, reduced physical activity, and greater …

Renewal Of Cocaine Seeking Using Social And Nonsocial Contextual Stimuli, Bree A. Humburg, Michael T. Bardo

Psychology Faculty Publications

Rationale Various nonsocial cues have been used as stimuli to examine the contextual control of drug seeking behavior, but little is known about the role of social stimuli.

Objectives This study determined if renewal of cocaine seeking is differentially controlled using a context consisting of either a social peer and/or house light illumination.

Methods In Experiment 1, male and female rats trained to self-administer cocaine in the presence of a same-sex social peer and house light illumination (context A). Following self-administration, rats were randomly assigned to either an AAA (control) or ABA (renewal) group for extinction. For AAA rats, extinction …

Comparison Of Laboratory Scale Bourbon Whiskey Mashing And Fermentation To Pilot Scale, Ryan C. Sarhan, Brad J. Berron, Czarena L. Crofcheck, Glenna Joyce Welsko, Tyler J. Barzee

Biosystems and Agricultural Engineering Faculty Publications

Why the work was done: Laboratory scale methods are useful for optimising grain spirit production. While small scale methods exist, comparisons between conventional, simultaneous saccharification and fermentation, and distillery scale production are lacking. Further, there is limited understanding of how these methods affect the rheological properties of the mash and flavour compounds from fermentation. This study compared conventional and simultaneous saccharification and fermentation mashing methods to a pilot scale distillery to establish a standard laboratory method for simulating industrial bourbon production.

How the work was done: Two mashing methods for bourbon whiskey were compared: simultaneous saccharification and fermentation versus conventional …

A Community Effort To Develop Common Data Elements For Pre-Clinical Spinal Cord Injury Research., Britt A. Fedor, Abel Torres-Espin, Romana Vavrek, Maryann E. Martone, John L. Bixby, John C. Gensel, Vance Lemmon, Jeffrey S. Grethe, J. Russel Huie, Adam R. Ferguson, Karim Fouad, The Preclinical Sci Common Data Elements (Cde) Workshop Participants

Spinal Cord and Brain Injury Research Center Faculty Publications

For nearly 350 years, the process of disseminating scientific knowledge has remained largely unchanged. Scientists conduct experiments, analyze the data, and publish their findings in the form of scientific articles. Since the turn of the century, this process has been challenged by numerous open science and data sharing efforts to enhance transparency, reproducibility, and replicability of scientific research. Big data approaches, together with machine learning and artificial intelligence, are frequently used to gain insight into the ever-growing complexity of biological systems and biomedical research. To utilize these approaches and harness the continuously increasing computational power requires data to be both …

Cross-Species Comparisons Between Pigs And Mice Reveal Conserved Sex-Specific Intraspinal Inflammatory Responses After Spinal Cord Injury, Reena Kumari, Gabrielle V. Hammers, Robert H. Hammons, Andrew N. Stewart, Steven M. Maclean, Tracy Niedzielko, Lonnie E. Schneider, Candace L. Floyd, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model.

Methods Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury.

Results SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing …

Bilirubin Hepatic And Intestinal Transport And Catabolism: Physiology, Pathophysiology, And Benefits, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Terry D. Hinds, Jr., Wang-Hsin Lee

Pharmacology and Nutritional Sciences Faculty Publications

Bilirubin, a metabolite derived from heme degradation, has traditionally been regarded as a waste product and a marker of liver injury. However, increasing evidence suggests that bilirubin also functions as a hormone, and reduced levels are associated with metabolic dysfunction. Studies have shown a strong association between low circulating bilirubin levels and an increased risk of metabolic disorders and cardiovascular disease. To advance bilirubin-based treatment strategies, it is essential to elucidate the mechanisms underlying bilirubin transport and metabolism. Therefore, we provide an in-depth discussion of bilirubin production and its subsequent fates, with a particular focus on the transport between the …

Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Affordable Miniaturized Speckle Contrast Diffuse Correlation Tomography Device For Depth-Sensitive Mapping Of Cerebral Blood Flow In Rodents, Fatemeh Hamedi, Faezeh Akbari, Mehrana Mohtasebi, Chong Huang, Li Chen, Lei Chen, Guoqiang Yu

Biomedical Engineering Faculty Publications

Significance: Continuous and longitudinal monitoring of cerebral blood flow (CBF) is critical for understanding brain pathophysiology and guiding interventions. Although rodents are the primary models in neuroscience, existing imaging modalities often fail to provide the optimal combination of low cost, high spatiotemporal resolution, wide head coverage, and sufficient penetration depth for small-animal brain imaging.

Aim: Leveraging a clinical speckle contrast diffuse correlation tomography (scDCT) system, we aimed to develop an affordable, user-friendly, fast, and miniaturized scDCT (mini-scDCT) device tailored for depth-sensitive CBF imaging in small rodents.

Approach: The mini-scDCT replaces bulky and costly optoelectronic components with compact, low-cost alternatives while …

A 40-Week Phase 2b Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating The Safety And Efficacy Of Memantine In Amyotrophic Lateral Sclerosis, Salman Bhai, Todd Levine, Dan Moore, Robert Bowser, Andrew J. Heim, Maureen Walsh, Aziz Shibani, Zachary Simmons, James Grogan, Namita A. Goyal, Raghav Govindarajan, Yessar Hussain, Tania Papsdorf, Tiffany Schwasinger-Schmidt, Nick Olney, Kim Goslin, Michael Pulley, Edward J. Kasarskis, Michael Weiss, Susan W. Katz, Suzan Moser, Duaa Jabari, Omar Jawdat, Jeffrey Statland, Mazen M. Dimachkie, Richard Barohn, Neuromuscular Study Group And Western Als Consortium Memantine Als Study Group

Neurology Faculty Publications

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio …

You’Re On Fire: Social Skills Training To Increase Sportsmanship For Teenagers With Disabilities, Madeline K. Wainwright

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

This study presents findings from a multiple probe design that evaluated the effects of social skills training as a method of teaching an increase of good sportsmanship, more particularly compliments of gameplay, for individuals with intellectual disabilities. The research included three U.S. high school students with intellectual disabilities and the data was analyzed across conditions. Following mastery criterion, generalization sessions across contexts were conducted. All participants acquired complimenting behavior through social skills training. However, none of the participants were able to generalize the skill to different contexts. Results and directions for future research regarding generalization in replication and use of …

Evaluating A Naturalistic Language Intervention With Students With Complex Communication Needs In An Elementary Classroom, Kristina M. Johnson

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Communication is an essential skill for all students, but specifically for students with moderate to severe disabilities. Through communication, our students with disabilities express their wants and need, make and maintain relationships, and participate in daily activities at home, school, and in the community. Play is a natural and motivating activity that encourages communication in all settings. Thus, I looked at using naturalistic language intervention (NLI) as an intervention strategy to increase expressive communication skills in my students with expressive language deficits. This project aimed to increase expressive communication skills in three elementary students with moderate to severe disabilities by …

Effects Of Dietary Energy Source And Stress On Equine Intestinal Permeability And Inflammation, Amanda R. Bauman

Theses and Dissertations--Animal and Food Sciences

Dietary concentrate is often provided to exercising horses to meet energy requirements. However, both high-starch and high-fat diets may be associated with alterations in intestinal barrier function. To investigate this, 32 mature horses were fed one of four isocaloric dietary concentrate treatments (n = 8 per treatment): 1) a concentrate with cracked corn providing 4 g starch⋅kg BW^-1⋅d^-1 and 0.2 g fat⋅kg BW^-1⋅d^-1 (CC), 2) a concentrate with puffed corn providing 4 g starch⋅kg BW^-1⋅d^-1 and 0.2 g fat⋅kg BW^-1⋅d^-1 (PC), 3) a concentrate with puffed corn and …

Metabolic And Barrier Function In Response To Β-Caryophyllene In Intestinal Epithelial Cells, Hannah Scroggins

Theses and Dissertations--Animal and Food Sciences

Butyrate, a short-chain fatty acid, regulates cellular metabolism and energy status in intestinal epithelial cells. β-caryophyllene (BCP) is a plant-derived compound that may provide advantageous effects on intestinal barrier function and nutrient utilization. The goal of this thesis was to investigate the effects of BCP on butyrate utilization and metabolism in intestinal epithelial cells. Throughout this thesis, Caco-2 cells in hanging inserts in multi-well plates were used as a model for the intestinal barrier. One study was conducted to investigate the effect of BCP on butyrate utilization and barrier function in intestinal epithelial cells. A second study aimed to elucidate …

Comparison Of Sheep And Cattle Rumen Microbiological And Physiological Responses To An Abrupt Transition From A High-Forage To A High-Concentrate Diet, Katherine Purvis

Theses and Dissertations--Animal and Food Sciences

Sheep and cattle are often used interchangeably due to having the same gastrointestinal anatomy; however literature directly comparing the two species is minimal. Previous in vitro studies have pointed towards potential species differences in rumen carbohydrate utilization and acidosis susceptibility. The objective of this study was to evaluate in vivo microbiological and physiological responses of wethers and steers when abruptly transitioned from a high-forage to a high-concentrate diet. We hypothesized there are differences between species in response to abrupt dietary transition with respect to intake, rumen microbiology, and the rumen environment. Individually housed, rumen cannulated purebred Polypay wethers (n = …

Nicorandil Treatment Improves Survival And Spatial Learning In Aged Granulin Knockout Mice, Dana M. Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling X. Fister, Colin B. Rogers, Pradoldej Sompol, David K. Powell, Indumati Patel, Christopher M. Norris, Kathryn E. Saatman, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the “K⁺ATP” channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …