Physiology Commons^™

Bmal1 Mediates Sex-Specific Circadian Regulation Of Cardiac Ion Channels And Temporal Arrhythmia Vulnerability, Brian P. Delisle, Ezekiel Rozmus, Abhilash Prabhat, Spencer B. Procopio, Xiping Zhang, Emilia Entcheva, Karyn A. Esser, Elizabeth Schroder

Physiology Faculty Publications

No abstract provided.

C/Ebpα Is Essential For Gonadal But Not Inguinal White Adipose Tissue Formation In Mice, Krista Y. Hu, Yu-Lin Ma, Esme A. Dodge, Olivia A. B. Maguire, Caio V. Matias, Ryan K. Barney, Hector S. Himede, Juliana Gomez Pardo, Miriam Cepeda, Scott M. Gordon, Robert C. Bauer

Physiology Faculty Publications

Objective: The distribution of excess white adipose tissue (WAT) in obesity correlates with risk for comorbidities. Thus, understanding depot-specific WAT developmental mechanisms is translationally relevant. SNPs near the gene CEBPA associate with waist to hip ratio, and while C/EBPα is a recognized regulator of adipogenesis, there is no previously known role for C/EBPα in regulating adipose distribution.

Methods: We crossed Cebpa floxed mice to the AdipoQ-Cre transgenic mouse strain, generating mice with adipocyte-specific knockout of Cebpa (Cebpa_ASKO). Mice were phenotyped on a chow diet and after prolonged high-fat diet (HFD) feeding.

Results: Cebpa_ASKO mice almost entirely lack gonadal …

Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle

Physiology Faculty Publications

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. CAN is characterized by impaired cardiovascular autonomic control and is associated with increased mortality, especially among women with type 2 diabetes. Identifying environmental factors that exacerbate the CAN-associated phenotype may reveal modifiable strategies to reduce cardiovascular risk.

Nighttime light exposure is a novel cardiovascular risk factor. Among ∼90,000 individuals, greater nighttime light exposure correlated with increased atrial fibrillation and heart failure risk. Light at night disrupts sympathovagal balance and elevates nocturnal heart rate in humans. Dim light at night similarly disrupts autonomic regulation of heart rate in mice. We …

Early Microglial Response To Amyloid Plaques Drives Sleep Loss In Alzheimer’S Disease, Nicholas J. Constantino, Riley E. Irmen, Matthew J. Lanning, Sierra M. Turner, Clair C. Ashley, Caitlin M. Carroll, Evan M. Neary, Dave Rubinow, J. Andy Snipes, Shannon L. Macauley

Physiology Faculty Publications

Introduction: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear.

Methods: Electroencephalography/electromyography (EEG/EMG) recordings, quantitative EEG analysis, and sleep deprivation were performed in APPswe/PSEN1dE9 (APP/PS1) mice at different stages of pathology relative to normal aging. Amyloid burden and microglial density were quantified with whole-brain light-sheet microscopy. CSF1R-mediated microglial depletion explored effects of microglia on sleep loss.

Results: Amyloid plaques caused non–rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with …

Ceramide Homeostasis In Hepatic Lipid Droplets, Leobarda Robles-Martinez, Kylie H. Morin, Mariana Nikolova‑Karakashian

Physiology Faculty Publications

Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulators of cellular stress response that buffer excess free fats and protect cells from lipotoxicity. Ceramide is a bioactive lipid that accumulates in metabolic tissues during fat oversupply. Emerging evidence suggests that sphingolipids and sphingolipid-metabolizing enzymes are found in the LDs and affect LD biogenesis and functions. This article aims to summarize the evidence, delineate some plausible functions of ceramide in hepatic LD biogenesis, and illustrate some of …

Distinct Odorant Receptor Response Patterns To Aliphatic Odorants In Freely Behaving Mice, Claire A. De March, Patrick Breheny, William B. Titlow, Hiroaki Matsunami, Timothy S. Mcclintock

Physiology Faculty Publications

In mammals, odors are encoded by a combinatorial code determined by the pattern of responses across hundreds of odorant receptors expressed monogenically and monoallelically in olfactory sensory neurons. The compositions of these receptor response patterns are largely unknown and overlap between them has yet to be explored. Activity-dependent reporter gene expression in freely behaving S100a5-tauGFP mice allowed capture of activated olfactory sensory neurons and identified 168 receptors responsive to moderate concentrations of 1 or more of 12 aliphatic (5 to 8 carbons) ketones, alcohols, and carboxylic acids. These 12 response patterns are remarkably different, with only 19% of the receptors …

Feeding- And Light-Cycle Synergistically Regulate Mouse Blood Pressure Daily Rhythm Via Bmal1-Dependent And Independent Mechanisms, Tianfei Hou, Wen Su, Aaron Chacon, An-Hsuan Lin, Zhenheng Guo, Ming C. Gong

Physiology Faculty Publications

Cardiovascular health requires the orchestration of the daily rhythm of blood pressure (BP), which responds to changes in light exposure and dietary patterns. Whether rhythmic light and feeding can modulate daily BP rhythm directly or via modulating intrinsic core clock gene Bmal1 is unknown. Using inducible global Bmal1 knockout mice (iBmal1KO), we explored the impact of rhythmic light, rhythmic feeding, or their combination on various physiological parameters. Daily rhythms of BP, heart rate, and locomotor activity were monitored via radiotelemetry, while food intake patterns were tracked using the BioDAQ system. Respiratory exchange ratio (RER) and energy expenditure (EE) were assessed …

Advancements In Apoe And Dementia Research: Highlights From The 2023 Aaic Advancements: Apoe Conference., Courtney M Kloske, Michael E Belloy, Elizabeth E Blue, Gregory R Bowman, Maria C Carrillo, Xiaoying Chen, Ornit Chiba-Falek, Albert A Davis, Gilbert Di Paolo, Francesca Garretti, David Gate, Lesley R. Golden, Jay W Heinecke, Joachim Herz, Yadong Huang, Costantino Iadecola, Lance A Johnson, Takahisa Kanekiyo, Celeste M Karch, Anastasia Khvorova, Sascha J Koppes-Den Hertog, Bruce T Lamb, Paige E Lawler, Yann Le Guen, Alexandra Litvinchuk, Chia-Chen Liu, Simin Mahinrad, Edoardo Marcora, Claudia Marino, Danny M Michaelson, Justin J Miller, Josh M. Morganti, Priyanka S Narayan, Michel S Naslavsky, Marlies Oosthoek, Kapil V Ramachandran, Abhirami Ramakrishnan, Ana-Caroline Raulin, Aiko Robert, Rasha N M Saleh, Claire Sexton, Nilomi Shah, Francis Shue, Isabel J Sible, Andrea Soranno, Michael R Strickland, Julia Tcw, Manon Thierry, Li-Huei Tsai, Ryan A Tuckey, Jason D Ulrich, Rik Van Der Kant, Na Wang, Cheryl L Wellington, Stacie C Weninger, Hussein N Yassine, Na Zhao, Guojun Bu, Alison M Goate, David M Holtzman

Physiology Faculty Publications

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.

METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates …

A Practical Guide To Data Management And Sharing For Biomedical Laboratory Researchers., K Fouad, R Vavrek, M C Surles-Zeigler, J R Huie, H L Radabaugh, G G Gurkoff, U Visser, J S Grethe, M E Martone, A R Ferguson, John C. Gensel, A Torres-Espin

Physiology Faculty Publications

Effective data management and sharing have become increasingly crucial in biomedical research; however, many laboratory researchers lack the necessary tools and knowledge to address this challenge. This article provides an introductory guide into research data management (RDM), and the importance of FAIR (Findable, Accessible, Interoperable, and Reusable) data-sharing principles for laboratory researchers produced by practicing scientists. We explore the advantages of implementing organized data management strategies and introduce key concepts such as data standards, data documentation, and the distinction between machine and human-readable data formats. Furthermore, we offer practical guidance for creating a data management plan and establishing efficient data …

Asthmatic Patients With High Serum Amyloid A Have Proinflammatory Hdl: Implications For Augmented Systemic And Airway Inflammation., Xianglan Yao, Maryann Kaler, Xuan Qu, Rama Satyanarayana Raju Kalidhindi, Denis Sviridov, Amaury Dasseux, Eric Barr, Karen Keeran, Kenneth R. Jeffries, Zu-Xi Yu, Meixia Gao, Scott Gordon, Amisha V. Barochia, Joni Mills, Shahid Shahid, Nargues A. Weir, Or Kalchiem-Dekel, Patricia Theard, Martin P. Playford, Mario Stylianou, Wendy Fitzgerald, Alan T. Remaley, Stewart J. Levine

Physiology Faculty Publications

RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity.

OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory.

METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice.

RESULTS: …

Acute Gastrointestinal Permeability After Traumatic Brain Injury In Mice Precedes A Bloom In Akkermansia Muciniphila Supported By Intestinal Hypoxia, Anthony J. Desana, Steven Estus, Terrence A. Barrett, Kathryn E. Saatman

Physiology Faculty Publications

Traumatic brain injury (TBI) increases gastrointestinal morbidity and associated mortality. Clinical and preclinical studies implicate gut dysbiosis as a consequence of TBI and an amplifier of brain damage. However, little is known about the association of gut dysbiosis with structural and functional changes of the gastrointestinal tract after an isolated TBI. To assess gastrointestinal dysfunction, mice received a controlled cortical impact or sham brain injury and intestinal permeability was assessed at 4 h, 8 h, 1 d, and 3 d after injury by oral administration of 4 kDa FITC Dextran prior to euthanasia. Quantification of serum fluorescence revealed an acute, …

Advanced Age And Neurotrauma Diminish Glutathione And Impair Antioxidant Defense After Spinal Cord Injury, Andrew N. Stewart, Ethan P. Glaser, Caitlin A. Mott, William M. Bailey, Patrick G. Sullivan, Samir P. Patel, John C. Gensel

Physiology Faculty Publications

Advanced age at the time of spinal cord injury (SCI) exacerbates damage from reactive oxygen species (ROS). Mechanisms underlying this age-dependent response are not well understood and may arise from decreased antioxidant defense. We investigated how spinal cord levels of the antioxidant glutathione (GSH), and its regulation, change with age and SCI. GSH is used by GSH peroxidase to sequester ROS and is recycled by GSH reductase. Male and female, 4- and 14-month-old (MO) mice received a 60 kDyn contusion SCI, and the levels of GSH and its regulatory enzymes were evaluated at one and three days post-injury (dpi). The …

Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus

Physiology Faculty Publications

Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we evaluated effects of APOE heterozygosity and tested whether these overall results extended to mice maintained under ideal conditions for microbiome analyses. To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, homozygous APOE3 mice were crossed to homozygous APOE2 or homozygous APOE4 mice prior to the study, and the resulting …

Inhibition Of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade And Promotes Recovery After Spinal Cord Injury, Chen Guang Yu, Vimala Bondada, Hina Iqbal, Kate L. Moore, John C. Gensel, Subbarao Bondada, James W. Geddes

Physiology Faculty Publications

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib …

Evidence Of Myomir Regulation Of The Pentose Phosphate Pathway During Mechanical Load-Induced Hypertrophy, Taylor Valentino, Vandre C. Figueiredo, C. Brooks Mobley, John J. Mccarthy, Ivan J. Vechetti Jr.

Physiology Faculty Publications

Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved …

Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif

Physiology Faculty Publications

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …

Editorial: Perturbations In Metabolic Cues: Implications For Adverse Cardiac Function Leading To Sudden Cardiac Death, Brian P. Delisle, Ademuyiwa S. Aromolaran

Physiology Faculty Publications

No abstract provided.

Fibroblast Growth Factor 19 Increases The Excitability Of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice, Jordan B. Wean, Bret N. Smith

Physiology Faculty Publications

Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV …

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Editorial: The Metabolism Of The Neuron-Glia Unit, Yannick Poitelon, Lance A. Johnson, Marie-Ève Tremblay

Physiology Faculty Publications

No abstract provided.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Dietary And Pharmacologic Manipulations Of Host Lipids And Their Interaction With The Gut Microbiome In Non-Human Primates, Jennifer M. Lang, Leslie R. Sedgeman, Lei Cai, Joseph D. Layne, Zhen Wang, Calvin Pan, Richard Lee, Ryan E. Temel, Aldons J. Lusis

Physiology Faculty Publications

The gut microbiome influences nutrient processing as well as host physiology. Plasma lipid levels have been associated with the microbiome, although the underlying mechanisms are largely unknown, and the effects of dietary lipids on the gut microbiome in humans are not well-studied. We used a compilation of four studies utilizing non-human primates (Chlorocebus aethiops and Macaca fascicularis) with treatments that manipulated plasma lipid levels using dietary and pharmacological techniques, and characterized the microbiome using 16S rDNA. High-fat diets significantly reduced alpha diversity (Shannon) and the Firmicutes/Bacteroidetes ratio compared to chow diets, even when the diets had different compositions …

Intravesical Cd74 And Cxcr4, Macrophage Migration Inhibitory Factor (Mif) Receptors, Mediate Bladder Pain, Shaojing Ye, Fei Ma, Dlovan F. D. Mahmood, Katherine L. Meyer-Siegler, Raymond E. Menard, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.

METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Cardiomyocyte Deletion Of Bmal1 Exacerbates Qt- And Rr-Interval Prolongation In Scn5a+/Δkpq Mice, Elizabeth A. Schroder, Jennifer L. Wayland, Kaitlyn M. Samuels, Syed F. Shah, Don E. Burgess, Tanya S. Seward, Claude S. Elayi, Karyn A. Esser, Brian P. Delisle

Physiology Faculty Publications

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the …

Hypertrophic Cardiomyopathy Β-Cardiac Myosin Mutation (P710r) Leads To Hypercontractility By Disrupting Super Relaxed State, Alison Schroer Vander Roest, Chao Liu, Makenna M. Morck, Kristina Bezold Kooiker, Gwanghyun Jung, Dan Song, Aminah Dawood, Arnav Jhingran, Gaspard Pardon, Sara Ranjbarvaziri, Giovanni Fajardo, Mingming Zhao, Kenneth S. Campbell, Beth L. Pruitt, James A. Spudich, Kathleen M. Ruppel, Daniel Bernstein

Physiology Faculty Publications

Hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, associated with over 1,000 mutations, many in β-cardiac myosin (MYH7). Molecular studies of myosin with different HCM mutations have revealed a diversity of effects on ATPase and load-sensitive rate of detachment from actin. It has been difficult to predict how such diverse molecular effects combine to influence forces at the cellular level and further influence cellular phenotypes. This study focused on the P710R mutation that dramatically decreased in vitro motility velocity and actin-activated ATPase, in contrast to other MYH7 mutations. Optical trap measurements of single myosin molecules revealed …

Igf1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent On Mtor, Erica L. Littlejohn, Anthony J. Desana, Hannah C. Williams, Rudy T. Chapman, Binoy Joseph, Jelena A. Juras, Kathryn E. Saatman

Physiology Faculty Publications

Adult hippocampal neurogenesis is stimulated acutely following traumatic brain injury (TBI). However, many hippocampal neurons born after injury develop abnormally and the number that survive long-term is debated. In experimental TBI, insulin-like growth factor-1 (IGF1) promotes hippocampal neuronal differentiation, improves immature neuron dendritic arbor morphology, increases long-term survival of neurons born after TBI, and improves cognitive function. One potential downstream mediator of the neurogenic effects of IGF1 is mammalian target of rapamycin (mTOR), which regulates proliferation as well as axonal and dendritic growth in the CNS. Excessive mTOR activation is posited to contribute to aberrant plasticity related to posttraumatic epilepsy, …

Acute Inflammatory Profiles Differ With Sex And Age After Spinal Cord Injury, Andrew N. Stewart, John L. Lowe, Ethan P. Glaser, Caitlin A. Mott, Ryan K. Shahidehpour, Katelyn E. Mcfarlane, William M. Bailey, Bei Zhang, John C. Gensel

Physiology Faculty Publications

Background

Sex and age are emerging as influential variables that affect spinal cord injury (SCI) recovery. Despite a changing demographic towards older age at the time of SCI, the effects of sex or age on inflammation remain to be elucidated. This study determined the sex- and age-dependency of the innate immune response acutely after SCI.

Methods

Male and female mice of ages 4- and 14-month-old received T9 contusion SCI and the proportion of microglia, monocyte-derived macrophages (MDM), and neutrophils surrounding the lesion were determined at 3- and 7-day post-injury (DPI) using flow cytometry. Cell counts of microglia and MDMs were …

The Effects Of Myelin On Macrophage Activation Are Phenotypic Specific Via Cpla2 In The Context Of Spinal Cord Injury Inflammation, Timothy J. Kopper, Bei Zhang, William M. Bailey, Kara E. Bethel, John C. Gensel

Physiology Faculty Publications

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin-mediated potentiation of pro-inflammatory macrophage activation. We hypothesized that cPLA₂ and myelin debris are key mediators of persistent pro-inflammatory macrophage responses after SCI. To test this, we examined spinal cord tissue 28-days after thoracic contusion SCI in 3-month-old female mice and observed both cPLA₂ activation and intracellular accumulation of lipid-rich myelin …

Lat1 Protein Content Increases Following 12 Weeks Of Resistance Exercise Training In Human Skeletal Muscle, Paul A. Roberson, Christopher Brooks Mobley, Matthew A. Romero, Cody T. Haun, Shelby C. Osburn, Petey W. Mumford, Christopher G. Vann, Rory A. Greer, Arny A. Ferrando, Michael D. Roberts

Physiology Faculty Publications

Introduction: Amino acid transporters are essential for cellular amino acid transport and promoting protein synthesis. While previous literature has demonstrated the association of amino acid transporters and protein synthesis following acute resistance exercise and amino acid supplementation, the chronic effect of resistance exercise and supplementation on amino acid transporters is unknown. The purpose herein was to determine if amino acid transporters and amino acid metabolic enzymes were related to skeletal muscle hypertrophy following resistance exercise training with different nutritional supplementation strategies.

Methods: 43 college-aged males were separated into a maltodextrin placebo (PLA, n = 12), leucine (LEU, n = 14), …