Physiology Commons^™

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O’Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

Molecular and Cellular Biochemistry Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness …

Macrophage Migration Inhibitory Factor Mediates Protease-Activated Receptor 4-Induced Bladder Pain Through Urothelial High Mobility Group Box 1, Fei Ma, Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

Macrophage migration inhibitory factor (MIF) mediates pain although the mechanisms are not well understood. Urothelial activation of protease activated receptor 4 (PAR4) results in urothelial MIF release, urothelial high mobility group box 1 (HMGB1) release and bladder pain in mice without bladder inflammation. All three effects are prevented by MIF inhibition while intravesical disulfide HMGB1 alone can induce bladder pain. This study utilizes genetic MIF deletion to determine whether MIF mediates PAR4-induced bladder pain and is upstream of HMGB1-induced bladder pain. Wild type (C57/BL6) and MIF knockout (KO) mice were treated with intravesical PAR4 activating peptide or disulfide HMGB1 and …

Acute Resistance Exercise Induces Sestrin2 Phosphorylation And P62 Dephosphorylation In Human Skeletal Muscle, Nina Zeng, Randall F. D'Souza, Vandre C. Figueiredo, James F. Markworth, Llion A. Roberts, Jonathan M. Peake, Cameron J. Mitchell, David Cameron-Smith

Center for Muscle Biology Faculty Publications

Sestrins (1, 2, 3) are a family of stress-inducible proteins capable of attenuating oxidative stress, regulating metabolism, and stimulating autophagy. Sequestosome1 (p62) is also a stress-inducible multifunctional protein acting as a signaling hub for oxidative stress and selective autophagy. It is unclear whether Sestrin and p62^Ser403 are regulated acutely or chronically by resistance exercise (RE) or training (RT) in human skeletal muscle. Therefore, the acute and chronic effects of RE on Sestrin and p62 in human skeletal muscle were examined through two studies. In Study 1, nine active men (22.1 ± 2.2 years) performed a bout of single-leg strength …

Methylglyoxal Requires Ac1 And Trpa1 To Produce Pain And Spinal Neuron Activation, Ryan B. Griggs, Don E. Laird, Renee R. Donahue, Weisi Fu, Bradley K. Taylor

Physiology Faculty Publications

Methylglyoxal (MG) is a metabolite of glucose that may contribute to peripheral neuropathy and pain in diabetic patients. MG increases intracellular calcium in sensory neurons and produces behavioral nociception via the cation channel transient receptor potential ankyrin 1 (TRPA1). However, rigorous characterization of an animal model of methylglyoxal-evoked pain is needed, including testing whether methylglyoxal promotes negative pain affect. Furthermore, it remains unknown whether methylglyoxal is sufficient to activate neurons in the spinal cord dorsal horn, whether this requires TRPA1, and if the calcium-sensitive adenylyl cyclase 1 isoform (AC1) contributes to MG-evoked pain. We administered intraplantar methylglyoxal and then evaluated …

Hyperhomocysteinemia-Induced Gene Expression Changes In The Cell Types Of The Brain, Erica M. Weekman, Abigail E. Woolums, Tiffany L. Sudduth, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet …

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Validation Of The Short Recovery Stress Scale Questionnaire During Women’S Volleyball In-Season Training, Asher Flynn, Joseph Walters, Henry Lang, Alec Perkins, Jacob Goodin, Caleb D. Bazyler

ETSU Faculty Works

No abstract provided.

Resting Hormone Alterations And Injuries: Block Vs “Daily Undulating Periodization” Weight-Training Among Division I Track And Field Athletes, Keith B. Painter, Gregory N. Haff, Travis Triplett, Charles A. Stuart, Guy Hornsby, Michael W. Ramsey, Caleb D. Bazyler, Michael H. Stone

ETSU Faculty Works

No abstract provided.

Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Physiology Faculty Publications

The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP‐21. We previously demonstrated that TLQP‐21 elicits hyperalgesia and contributes to nerve injury‐induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP‐21. We propose a novel neuroimmune signaling pathway involving TLQP‐21‐induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual‐ligand activation of C3aR1 by a neuropeptide (TLQP‐21) and an immune mediator (C3a) represents a …

Physiological And Biomechanical Responses Of Highly Trained Distance Runners To Lower-Body Positive Pressure Treadmill Running, Kyle Barnes, Jessica N. Janecke

Funded Articles

Background: As a way to train at faster running speeds, add training volume, prevent injury, or rehabilitate after an injury, lower-body positive pressure treadmills (LBPPT) have become increasingly commonplace among athletes. However, there are conflicting evidence and a paucity of data describing the physiological and biomechanical responses to LBPPT running in highly trained or elite caliber runners at the running speeds they habitually train at, which are considerably faster than those of recreational runners. Furthermore, data is lacking regarding female runners’ responses to LBPPT running. Therefore, this study was designed to evaluate the physiological and biomechanical responses to LBPPT …

Current Research And Statistical Practices In Sport Science And A Need For Change, Jake R. Bernards, Kimitake Sato, G. Gregory Haff, Caleb D. Bazyler

ETSU Faculty Works

Current research ideologies in sport science allow for the possibility of investigators producing statistically significant results to help fit the outcome into a predetermined theory. Additionally, under the current Neyman-Pearson statistical structure, some argue that null hypothesis significant testing (NHST) under the frequentist approach is flawed, regardless. For example, a p-value is unable to measure the probability that the studied hypothesis is true, unable to measure the size of an effect or the importance of a result, and unable to provide a good measure of evidence regarding a model or hypothesis. Many of these downfalls are key questions researchers strive …

Abnormal Contractility In Human Heart Myofibrils From Patients With Dilated Cardiomyopathy Due To Mutations In Ttn And Contractile Protein Genes, Petr G. Vikhorev, Natalia Smoktunowicz, Alex B. Munster, O'Neal Copeland, Sawa Kostin, Cecile Montgiraud, Andrew E. Messer, Mohammad R. Toliat, Amy Li, Cristobal G. Dos Remedios, Sean Lal, Cheavar A. Blair, Kenneth S. Campbell, Maya E. Guglin, Ralph Knoll, Steven B. Marston

Physiology Faculty Publications

Dilated cardiomyopathy (DCM) is an important cause of heart failure. Single gene mutations in at least 50 genes have been proposed to account for 25–50% of DCM cases and up to 25% of inherited DCM has been attributed to truncating mutations in the sarcomeric structural protein titin (TTNtv). Whilst the primary molecular mechanism of some DCM-associated mutations in the contractile apparatus has been studied in vitro and in transgenic mice, the contractile defect in human heart muscle has not been studied. In this study we isolated cardiac myofibrils from 3 TTNtv mutants, and 3 with contractile protein mutations (TNNI3 …

Primary Upper Urinary Tract Small Cell Carcinoma: A Case Series And Literature Review, Patrick J. Hensley, Amul A. Bhalodi, Shubham Gupta

Urology Faculty Publications

Background: Primary upper urinary tract small cell carcinoma (SCC) is exceedingly rare with < 30 cases reported in the literature. Little is known about the incidence, diagnosis, treatment, and outcomes in these patients. We present a series of three patients with primary upper tract SCC.

Case Presentation: Patient 1 is an 89-year-old Caucasian male who presented with hydroureteronephrosis and a mass in the proximal right ureter. Biopsy revealed SCC. Without further intervention, the patient died 2 months after his diagnosis. Patient 2 is a 67-year-old Caucasian female who underwent left laparoscopic nephroureterectomy for primary distal ureteral SCC, pT4N1M0. She developed lymphadenopathy and completed external beam radiation to the pelvis and four courses of cisplatin-based chemotherapy. She died from metastatic disease 7 months after diagnosis. Patient 3 is a 45-year-old female who underwent …

Calpain Inhibition Attenuates Adipose Tissue Inflammation And Fibrosis In Diet-Induced Obese Mice, Latha Muniappan, Aida Javidan, Weihua Jiang, Shayan Mohammadmoradi, Jessica J. Moorleghen, Wendy S. Katz, Anju Balakrishnan, Deborah A. Howatt, Venkateswaran Subramanian

Saha Cardiovascular Research Center Faculty Publications

Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. …

Functional Neuroplasticity In The Nucleus Tractus Solitarius And Increased Risk Of Sudden Death In Mice With Acquired Temporal Lobe Epilepsy, Isabel D. Derera, Brian P. Delisle, Bret N. Smith

Physiology Faculty Publications

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in individuals with refractory acquired epilepsy. Cardiorespiratory failure is the most likely cause in most cases, and central autonomic dysfunction has been implicated as a contributing factor to SUDEP. Neurons of the nucleus tractus solitarius (NTS) in the brainstem vagal complex receive and integrate vagally mediated information regarding cardiorespiratory and other autonomic functions, and GABAergic inhibitory NTS neurons play an essential role in modulating autonomic output. We assessed the activity of GABAergic NTS neurons as a function of epilepsy development in the pilocarpine-induced status epilepticus (SE) model of …

Deletion Of The Nr4a Nuclear Receptor Nor1 In Hematopoietic Stem Cells Reduces Inflammation But Not Abdominal Aortic Aneurysm Formation, Hua Qing, Karrie L. Jones, Elizabeth B. Heywood, Hong Lu, Alan Daugherty, Dennis Bruemmer

Pharmacology and Nutritional Sciences Faculty Publications

Background: The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously.

Methods: Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice. Low-density lipoprotein receptor-deficient (LDLr^−/−) mice were irradiated and reconstituted with hematopoietic stem cells obtained from NOR1−/− or wild-type littermate mice. Animals were infused with angiotensin II and fed a diet enriched in saturated …

No Difference In Myosin Kinetics And Spatial Distribution Of The Lever Arm In The Left And Right Ventricles Of Human Hearts, Divya Duggal, S. Requena, Janhavi Nagwekar, Sangram Raut, Ryan Rich, Hriday Das, Vipul Patel, Ignacy Gryczynski, Rafal Fudala, Zygmunt Gryczynski, Cheavar Blair, Kenneth S. Campbell, Julian Borejdo

Physiology Faculty Publications

The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. …

Maximum Strength, Rate Of Force Development, Jump Height, And Peak Power Alterations In Weightlifters Across Five Months Of Training, W. Guy Hornsby, Jeremy A. Gentles, Christopher J. Macdonald, Satoshi Mizuguchi, Michael W. Ramsey, Michael H. Stone

ETSU Faculty Works

The purpose of this monitoring study was to investigate how alterations in training affect changes in force-related characteristics and weightlifting performance. Subjects: Seven competitive weightlifters participated in the study. Methods: The weightlifters performed a block style periodized plan across 20 weeks. Force plate data from the isometric mid-thigh pull and static jumps with 0 kg, 11 kg, and 20 kg were collected near the end of each training block (weeks 1, 6, 10, 13, 17, and 20). Weightlifting performance was measured at weeks 0, 7, 11, and 20. Results: Very strong correlations were noted between weightlifting performances and isometric rate …

Decreased Triple Network Connectivity In Patients With Recent Onset Post-Traumatic Stress Disorder After A Single Prolonged Trauma Exposure, Yang Liu, Liang Li, Baojuan Li, Na Feng, Lihong Li, Xi Zhang, Hongbing Lu, Hong Yin

Publications and Research

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With an arterial spin labeling sequence, three networks were first identified using independent component analysis among 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. Then, the triple network connectivity was …

Psychosocial Functioning And The Cortisol Awakening Response: Meta-Analysis, P-Curve Analysis, And Evaluation Of The Evidential Value In Existing Studies, Ian Andres Boggero, Camelia E. Hostinar, Eric A. Haak, Michael L. M. Murphy, Suzanne C. Segerstrom

Psychology Faculty Publications

Cortisol levels rise immediately after awakening and peak approximately 30-45 minutes thereafter. Psychosocial functioning influences this cortisol awakening response (CAR), but there is considerable heterogeneity in the literature. The current study used p-curve and metaanalysis on 709 findings from 212 studies to test the evidential value and estimate effect sizes of four sets of findings: those associating worse psychosocial functioning with higher or lower cortisol increase relative to the waking period (CARi) and to the output of the waking period (AUCw). All four sets of findings demonstrated evidential value. Psychosocial predictors explained 1%-3.6% of variance in CARi and AUCw …

Adipose Tissue As A Site Of Toxin Accumulation, Erin Jackson, Robin C. Shoemaker, Nika Larian, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

We examine the role of adipose tissue, typically considered an energy storage site, as a potential site of toxicant accumulation. Although the production of most persistent organic pollutants (POPs) was banned years ago, these toxicants persist in the environment due to their resistance to biodegradation and widespread distribution in various environmental forms (e.g., vapor, sediment, and water). As a result, human exposure to these toxicants is inevitable. Largely due to their lipophilicity, POPs bioaccumulate in adipose tissue, resulting in greater body burdens of these environmental toxicants with obesity. POPs of major concern include polychlorinated biphenyls (PCBs), polychlorinated dibenzo‐p‐dioxins and furans …

Associative Learning Contributes To The Increased Water Intake Observed After Daily Injections Of Angiotensin Ii, Maggie Postolache, Jessica Santollo, Derek Daniels

Biology Faculty Publications

Daily injections of angiotensin II (AngII) cause a progressive increase of water intake that resembles a classically ascribed non-associative sensitization. Consistent with the presumption that the observed increase in intake was sensitization, we hypothesized that it resulted from a pharmacological interaction between AngII and its receptor. To test this hypothesis, and remove the influence of drinking itself, we implemented a delay in water access after injection of AngII (icv) on four consecutive ‘induction days,’ and then measured intake on the next day (‘test day’) when rats were allowed to drink immediately after AngII. The delay in water access effectively reduced …

What’S Food Got To Do With It?: The Host Mother’S Role In The Cultural Education Of Students Studying Abroad In The Rabat Medina, Isabel Bonhomme

Independent Study Project (ISP) Collection

The dynamic between studentsstudying abroad and the host families with whom they stay is significant to both the study abroad experience and the way people in receiving countries view those fromthe West. Through my research, my goal was to explore and reachafundamental comprehension of this global dynamic from the Moroccan perspective.Specifically, the purpose of this study is to gain a deeper understanding of the process of cultural exchange and absorption which occurs through the use of food. I draw conclusions from information attained through formal interviews of mothers who host American students studying abroad in Rabat, and supplement this with …

Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, …

Nutrients, Infectious And Inflammatory Diseases, Helieh S. Oz

Physiology Faculty Publications

No abstract provided.

There’S More Than One Way To Climb A Tree: Limb Length And Microhabitat Use In Lizards With Toe Pads, Travis J. Hagey, Scott Hart, Matthew Vickers, Luke J. Harmon, Lin Schwarzkopf

Biology

Ecomorphology links microhabitat and morphology. By comparing ecomorphological associations across clades, we can investigate the extent to which evolution can produce similar solutions in response to similar challenges. While Anolis lizards represent a well-studied example of repeated convergent evolution, very few studies have investigated the ecomorphology of geckos. Similar to anoles, gekkonid lizards have independently evolved adhesive toe pads and many species are scansorial. We quantified gecko and anole limb length and microhabitat use, finding that geckos tend to have shorter limbs than anoles. Combining these measurements with microhabitat observations of geckos in Queensland, Australia, we observed geckos using similar …

Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock

Internal Medicine Faculty Publications

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr^−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …

Intrathecal Administration Of Ayx2 Dna Decoy Produces A Long-Term Pain Treatment In Rat Models Of Chronic Pain By Inhibiting The Klf6, Klf9, And Klf15 Transcription Factors, Julien Mamet, Michael Klukinov, Scott Harris, Donald C. Manning, Simon Xie, Conrado Pascual, Bradley K. Taylor, Renee R. Donahue, David C. Yeomans

Physiology Faculty Publications

Background: Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive …

Brain Injury-Induced Synaptic Reorganization In Hilar Inhibitory Neurons Is Differentially Suppressed By Rapamycin, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in …