Medicine and Health Sciences Commons^™

Modeling Reveals The Dependence Of Hippocampal Neurogenesis Radiosensitivity On Age And Strain Of Rats, Eliedonna Cacao, Sidath Kapukotuwa, Francis A. Cucinotta

Health Physics & Diagnostic Sciences Faculty Publications

Cognitive dysfunction following radiation treatment for brain cancers in both children and adults have been correlated to impairment of neurogenesis in the hippocampal dentate gyrus. Various species and strains of rodent models have been used to study radiation-induced changes in neurogenesis and these investigations have utilized only a limited number of doses, dose-fractions, age and time after exposures conditions. In this paper, we have extended our previous mathematical model of radiation-induced hippocampal neurogenesis impairment of C57BL/6 mice to delineate the time, age, and dose dependent alterations in neurogenesis of a diverse strain of rats. To the best of our knowledge, …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Global Connectivity And Function Of Descending Spinal Input Revealed By 3d Microscopy And Retrograde Transduction, Zimei Wang, Brian Maunze, Yunfang Wang, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. This complexity presents a major challenge to interpreting functional outcomes from therapies that target supraspinal connectivity after injury or disease, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate that injection of AAV2-Retro to the cervical spinal cord of adult female mice results in highly efficient transduction of supraspinal populations throughout the brainstem, midbrain, and cortex. …

Impaired Object-Location Learning And Recognition Memory But Enhanced Sustained Attention In M2 Muscarinic Receptor-Deficient Mice, Carola Romberg, Susan Bartko, Jürgen Wess, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous …

The Psychological Science Accelerator: Advancing Psychology Through A Distributed Collaborative Network, Hannah Moshontz, Lorne Campbell, Charles R. Ebersole, Hans Ijzerman, Heather L. Urry, Patrick S. Forscher, Jon E. Grahe, Randy J. Mccarthy, Erica D. Musser, Jan Antfolk, Christopher M. Castille, Thomas Rhys Evans, Susann Fiedler, Jessica Kay Flake, Diego A. Forero, Steve M. Janssen, Justin Robert Keene, John Protzko, Balazs Aczel, Sara Álvarez Solas, Daniel Ansari, Dana Awlia, Ernest Baskin, Carlota Batres, Martha Lucia Borras-Guevara, Cameron Brick, Priyanka Chandel, Armand Chatard, William J. Chopik, David Clarance, Nicholas A. Coles, Katherine S. Corker

Brain and Mind Institute Researchers' Publications

Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta

School of Medicine Faculty Publications

No abstract provided.

Exploring The Neural Mechanisms Of Physics Learning, Jessica E. Bartley

FIU Electronic Theses and Dissertations

This dissertation presents a series of neuroimaging investigations and achievements that strive to deepen and broaden our understanding of human problem solving and physics learning. Neuroscience conceives of dynamic relationships between behavior, experience, and brain structure and function, but how neural changes enable human learning across classroom instruction remains an open question. At the same time, physics is a challenging area of study in which introductory students regularly struggle to achieve success across university instruction. Research and initiatives in neuroeducation promise a new understanding into the interactions between biology and education, including the neural mechanisms of learning and development. These …

Adenosine Signaling Through A1 Receptors Inhibits Chemosensitive Neurons In The Retrotrapezoid Nucleus, S. D. James, V. E. Hawkins, B. Falquetto, D. N. Ruskin, S. A. Masino, T. S. Moreira, M. L. Olsen, D. K. Mulkey

Faculty Scholarship

© 2018 James et al. A subset of neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating depth and frequency of breathing in response to changes in tissue CO 2 /H + . The activity of chemosensitive RTN neurons is also subject to modulation by CO 2 /H + -dependent purinergic signaling. However, mechanisms contributing to purinergic regulation of RTN chemoreceptors are not entirely clear. Recent evidence suggests adenosine inhibits RTN chemoreception in vivo by activation of A1 receptors. The goal of this study was to characterize effects of adenosine on chemosensitive RTN neurons and identify intrinsic …

Leveling The Playing Field: Supporting Neurodiversity Via Virtual Realities, Louanne E. Boyd, Kendra Day, Natalia Stewart, Kaitlyn Abdo, Kathleen Lamkin, Erik J. Linstead

Mathematics, Physics, and Computer Science Faculty Articles and Research

Neurodiversity is a term that encapsulates the diverse expression of human neurology. By thinking in broad terms about neurological development, we can become focused on delivering a diverse set of design features to meet the needs of the human condition. In this work, we move toward developing virtual environments that support variations in sensory processing. If we understand that people have differences in sensory perception that result in their own unique sensory traits, many of which are clustered by diagnostic labels such as Autism Spectrum Disorder (ASD), Sensory Processing Disorder, Attention-Deficit/Hyperactivity Disorder, Rett syndrome, dyslexia, and so on, then we …

Longitudinal Screening Detects Cognitive Stability And Behavioral Deterioration In Als Patients, Susan Woolley, Ray Goetz, Pam Factor-Litvak, Jennifer Murphy, Jonathan Hupf, Catherine Lomen-Hoerth, Howard Andrews, Daragh Heitzman, Richard Bedlack, Jonathan Katz, Richard Barohn, Eric Sorenson, Bjorn Oskarsson, Americo Fernandes Filho, Edward J. Kasarskis, Tahseen Mozaffar, Sharon Nations, Andrea Swenson, Agnes Koczon-Jaremko, Georgia Christodoulou, Hiroshi Mitsumoto

Neurology Faculty Publications

Objective. To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods. We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results. Participants with follow-up data had fewer baseline behavior problems compared to patients …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Common Sense And Common Nonsense: A Conversation About Mental Attitudes, Science, And Society, Daniel S. Levine

Psychology Faculty Publications

Daniel S. Levine's Common Sense and Common Nonsense observes human decision making, ethics, and social organization as illuminated by the scientific disciplines of neural network theory, neuroscience, experimental psychology, and dynamical systems theory. It is a book whose aim is advocacy as well as research. Its goal is to use an understanding of our brains and minds to better operationalize Aldous Huxley's admonition to "try to be a little kinder." It wanders over examples from sociology, politics, economics, religion, literature, and many other fields but looks at all as examples of a few common themes. The "common nonsense" of the …

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M. Ransohoff, Astrid E. Cardona

Department of Microbiology and Immunology Faculty Papers

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …

A Neuroimaging Web Interface For Data Acquisition, Processing And Visualization Of Multimodal Brain Images, Gabriel M. Lizarraga

FIU Electronic Theses and Dissertations

Structural and functional brain images are generated as essential modalities for medical experts to learn about the different functions of the brain. These images are typically visually inspected by experts. Many software packages are available to process medical images, but they are complex and difficult to use. The software packages are also hardware intensive. As a consequence, this dissertation proposes a novel Neuroimaging Web Services Interface (NWSI) as a series of processing pipelines for a common platform to store, process, visualize and share data. The NWSI system is made up of password-protected interconnected servers accessible through a web interface. The …

Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion.

METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient …

Developmental Chromatin Restriction Of Pro‐Growth Gene Networks Acts As An Epigenetic Barrier To Axon Regeneration In Cortical Neurons, Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age‐dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome‐wide maps of chromatin accessibility. When applied …

Coordination Of Inpatient And Outpatient Care For Neurology Patients Undergoing Epilepsy Monitoring, Sara Schrock, Michelle Beane, Kathryn Cope, Mark Parker, Suneela Nayak, Ruth Hanselman, Stephen Tyzik, Amy Sparks, Brendan Lilley

Operations Transformation

ORGANIZING A SYSTEM TO CONSOLIDATE EPILEPSY REFERRALS TO AN OUTPATIENT NEUROLOGY PRACTICE

An outpatient neurology practice was experiencing delayed or lost referrals for epilepsy monitoring. This delay was leading many patients to suffer unnecessary and unmanaged seizures and, in some cases, frequent trips to the emergency department.

As a result, a team consisting of the neurology practice and neuro-navigators used baseline metrics to demonstrate the current state of the problem and conducted a root cause analysis that outlined several causes. A number of countermeasures were initiated with the goal of decreasing referral misses.

Post the initiation of two KPIs, a …

Henle's Ligament: A Comprehensive Review Of Its Anatomy And Terminology Over Almost One And A Half Centuries., Raja Gnanadev, Joe Iwanaga, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Henle's ligament was first described by German physician and anatomist, Friedrich Henle, in 1871. This review article will cover Henle's original description of the ligament, historical changes in terminology, embryological studies of the ligament, and the clinical significance of Henle's ligament. This article has a particular focus on the variation in the terminology of this structure and the implications of this.

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Isolation Of Cerebral Capillaries From Fresh Human Brain Tissue, Anika M. S. Hartz, Julia A. Schulz, Brent S. Sokola, Stephanie E. Edelmann, Andrew N. Shen, Ralf G. Rempe, Yu Zhong, Nader El Seblani, Bjoern Bauer

Sanders-Brown Center on Aging Faculty Publications

Understanding blood-brain barrier function under physiological and pathophysiological conditions is critical for the development of new therapeutic strategies that hold the promise to enhance brain drug delivery, improve brain protection, and treat brain disorders. However, studying the human blood-brain barrier function is challenging. Thus, there is a critical need for appropriate models. In this regard, brain capillaries isolated from human brain tissue represent a unique tool to study barrier function as close to the human in vivo situation as possible. Here, we describe an optimized protocol to isolate capillaries from human brain tissue at a high yield and with consistent …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

A Neurotheological Approach To Spiritual Awakening, Andrew B. Newberg, Mark R. Waldman

Marcus Institute of Integrative Health Faculty Papers

A neurotheological approach suggests an analysis of spiritual awakening experiences by combining phenomenological data with neuroscience. This paper presents a synthesis combining information on the thoughts, feelings, and experiences associated with spiritual awakening experiences and neurophysiological data, primarily from neuroimaging studies, to help assess which brain structures might be associated with these experiences. Brain structures involved with emotions correlate with emotional responses while areas of the brain associated with the sense of self appear to correlate with the key feature of these experiences in which an individual loses the sense of self and feels intimately connected with God, universal consciousness, …

Validation And Optimisation Of A Touchscreen Progressive Ratio Test Of Motivation In Male Rats, Jonathan M. Hailwood, Christopher J. Heath, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Across species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only. Objectives: Touchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms. Methods: Separate groups …

Propofol Inhibits The Voltage-Gated Sodium Channel Nachbac At Multiple Sites., Yali Wang, Elaine Yang, Marta M. Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L. Klein, Roderic G. Eckenhoff, William P. Dailey, Manuel Covarrubias, Pei Tang, Yan Xu

Department of Neuroscience Faculty Papers

Voltage-gated sodium (Na_V) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic Na_V channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects …

Propofol Inhibits Prokaryotic Voltage-Gated Na+ Channels By Promoting Activation-Coupled Inactivation, Elaine Yang, Daniele Granata, Roderic G. Eckenhoff, Vincenzo Carnevale, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na⁺ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations …

Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim

Community & Environmental Health Faculty Publications

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and …

Ketogenic Diet Modulates Nad+-Dependent Enzymes And Reduces Dna Damage In Hippocampus, Marwa Elamin, David N. Ruskin, Susan A. Masino, Paola Sacchetti

Faculty Scholarship

© 2018 Elamin, Ruskin, Masino and Sacchetti. The ketogenic diet’s (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 …