Medicine and Health Sciences Commons^™

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 …

Different Behavioral Experiences Produce Distinctive Parallel Changes In, And Correlate With, Frontal Cortex And Hippocampal Global Post-Translational Histone Levels., Marissa Sobolewski, Garima Singh, Jay S. Schneider, Deborah A. Cory-Slechta

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While it is clear that behavioral experience modulates epigenetic profiles, it is less evident how the nature of that experience influences outcomes and whether epigenetic/genetic "biomarkers" could be extracted to classify different types of behavioral experience. To begin to address this question, male and female mice were subjected to either a Fixed Interval (FI) schedule of food reward, or a single episode of forced swim followed by restraint stress, or no explicit behavioral experience after which global expression levels of two activating (H3K9ac and H3K4me3) and two repressive (H3K9me2 and H3k27me3) post-translational histone modifications (PTHMs), were measured in hippocampus (HIPP) …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Modeling Impaired Hippocampal Neurogenesis After Radiation Exposure, Kapukotuwa Walawwe Sidath Chathuranga Kapukotuwa

UNLV Theses, Dissertations, Professional Papers, and Capstones

The birth of neuronal cells from neuronal stem cells is known as neurogenesis, and the granular cell layer of the dentate gyrus of hippocampus is one of the two regions in the brain this process occurs. Cognitive damages following radiation therapy for brain cancers in both children and adults have been linked to impairment of neurogenesis in the hippocampus. Studies followed using mice and rats as model animals have shown impairment in neurogenesis process following exposure to radiation. Obtaining experimental data for radiation-induced changes in neurogenesis in humans is very difficult. Model was developed and applied to mouse data previously; …

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

A Comparative Study On The Effect Of Aging On The Hippocampal Ca1 Area Of Male Albino Rat, Abeer E. El-Mehi, Fatma El-Nabawia A El-Safti, Rasha R. Selima, Wael B. El-Kholoy

Menoufia Medical Journal

Objectives This work aimed to study the effect of aging on the structure of the hippocampus in the adult and aged male albino rats. Background Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death, which accompanies advancing age. The hippocampal formation is one of the most common brain areas affected by aging in both humans and other mammalian species. Materials and methods Eighteen male albino rats were divided into …

Caffeine Consumption Disrupts Hippocampal Long-Term Potentiation In Freely Behaving Rats., J Harry Blaise, Jee Eun Park, Nicholas J Bellas, Thomas M Gitchell, Vy Phan

Faculty Scholarship

Caffeine, one of the most commonly consumed psychoactive substances in the world, has long been known to alter neurological functions, such as alertness, attention, and memory. Despite caffeine's popularity, systematic investigations of its effects on synaptic plasticity in the brain are still lacking. Here we used a freely behaving rodent model of long-term potentiation (LTP), a frequently studied form of synaptic plasticity, to assess the effects of caffeine consumption on hippocampal plasticity. LTP, which is a persistent increase in the strength of synaptic connections between neurons, is a cellular mechanism widely considered to underlie the processes of learning and memory. …

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory., Youssef Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein, Kathryn A. Davis, Gregory A. Worrell, Michal T. Kucewicz, Joel M. Stein, Richard Gorniak, Sandhitsu R. Das, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

The Effects Of Ketamine And Other Rapid Antidepressants On Hippocampal Circuits, Allie J. Widman

All ETDs from UAB

Major Depressive Disorder (MDD) in a common mental disorder that can impair cognitive functioning and negatively impact hippocampus. While several pharmacological treatments are currently available for MDD, most target the monoamine system, providing little variety in approaching treatment. Additionally, a large percentage of people with MDD have an inadequate response to this drug class, leaving them with little optimism of a full functional recovery. Recently, low-dose ketamine, an open-channel N-methyl D-aspartate receptor (NMDAR) antagonist, produced rapid antidepressant effects in humans, including people who do not respond to monoamine-based therapies, that lasted for days. The antidepressant-like behavioral effect of ketamine is …

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

All ETDs from UAB

Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …

Pathological Changes In Hippocampal Synaptic Transmission And Neuronal Function During Early Disease In The Novel Tgf344-Ad Rat Model, Lindsey Allyson Smith

All ETDs from UAB

Alzheimer’s disease (AD) is the leading cause of dementia in those 65 years and older and the 6th leading cause of death in the United Sates. Current treatments only target symptoms of the disease and cannot slow or halt disease progression. The novel and comprehensive TgF344-AD rodent model may bridge the translational gap previous animal models have failed to traverse by providing the platform to probe pre-lesion synapse dysfunction, which is thought to result primarily from increased levels of toxic soluble amyloid beta and hyperphosphorylated tau. The most recently developed model, the TgF344-AD rat was created in 2013 by insertion …