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Δfosb Regulates Gene Expression And Cognitive Dysfunction In A Mouse Model Of Alzheimer's Disease., Brian F Corbett, Jason C You, Xiaohong Zhang, Mark S Pyfer, Umberto Tosi, Daniel M Iascone, Iraklis Petrof, Anupam Hazra, Chia-Hsuan Fu, Gabriel S Stephens, Annie Ashok, Suzan Aschmies, Lijuan Zhao, Eric J Nestler, Jeannie Chin 2017 Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA

Δfosb Regulates Gene Expression And Cognitive Dysfunction In A Mouse Model Of Alzheimer's Disease., Brian F Corbett, Jason C You, Xiaohong Zhang, Mark S Pyfer, Umberto Tosi, Daniel M Iascone, Iraklis Petrof, Anupam Hazra, Chia-Hsuan Fu, Gabriel S Stephens, Annie Ashok, Suzan Aschmies, Lijuan Zhao, Eric J Nestler, Jeannie Chin

Department of Neuroscience

Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to ...


Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi 2017 Chapman University

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique ...


The Neural Encoding Of Reward In The Striatal-Pallidal Circuitry, Chung Lung Chan 2017 Marquette University

The Neural Encoding Of Reward In The Striatal-Pallidal Circuitry, Chung Lung Chan

Dissertations (2009 -)

Humans and animals are constantly exposed to external stimuli. The ability to process reward value of a stimulus is critical to guiding appropriate behavior and essential for survival. These processes are regulated by neuronal activity and neurochemical signaling in the reward circuitry, particularly in the nucleus accumbens (NAc). The NAc receives dopaminergic inputs from the midbrain ventral tegmental area (VTA) and sends GABAergic projections to the ventral pallidum (VP). Electrophysiological studies have characterized phasic neuronal responses in the NAc that differential encode appetitive and aversive taste stimuli. Exposure to an appetitive taste stimulus evoked predominantly phasic inhibitory responses in the ...


Presynaptic Lrp4 Promotes Synapse Number And Function Of Excitatory Cns Neurons., Timothy J. Mosca, David J. Luginbuhl, Irving E. Wang, Liqun Luo 2017 Thomas Jefferson University

Presynaptic Lrp4 Promotes Synapse Number And Function Of Excitatory Cns Neurons., Timothy J. Mosca, David J. Luginbuhl, Irving E. Wang, Liqun Luo

Department of Neuroscience

Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases synapse ...


Synaptic Computations In The Olfactory Bulb Glomerular Microcircuit, Christopher Vaaga 2017 Oregon Health & Science University

Synaptic Computations In The Olfactory Bulb Glomerular Microcircuit, Christopher Vaaga

Scholar Archive

No abstract provided.


A Whole Lot Of Shakin' Going On: Movement Disorders Caused By Brain Trauma, Jack E. Hubbard, Samuel D. Hodge, Jr. 2017 Temple University

A Whole Lot Of Shakin' Going On: Movement Disorders Caused By Brain Trauma, Jack E. Hubbard, Samuel D. Hodge, Jr.

Cleveland State Law Review

There has been a lot of publicity directed to the consequence of brain trauma, such as headaches forgetfulness, irritability, and depression. That is only part of the sequelae. A little-known but challenging result of brain trauma is the development of or aggravation of a movement disorder such as a tremor, dystonia, a tic, or Parkinson’s Disease.

A movement disorder is an all-encompassing term that refers to a constellation of neurological issues that cause involuntary or voluntary movements or abnormal positioning of a body part. Various regions of the brain interact with each other to control movements of the body ...


The Trial Lawyer And The Reptilian Brain: A Critique, Louis J. Sirico, Jr. 2017 Villanova University Charles Widger School of Law

The Trial Lawyer And The Reptilian Brain: A Critique, Louis J. Sirico, Jr.

Cleveland State Law Review

This Article brings together neuroscience, cultural symbolism, and the strategies of practicing lawyers to critique the reptile strategy, now popular among trial lawyers. The strategy directs the lawyer to trigger the reptilian brains of jurors so that they react instinctively to threats to themselves and their communities. When humans feel threatened, the reptilian brain, the most primitive part of the brain, takes charge and instinctively controls human conduct. Therefore, if a lawyer can make a juror feel threatened, the lawyer makes an appeal to the juror’s reptilian brain and virtually assures a victory. Thus, a lawyer’s argument should ...


The Acquisition And Analysis Of Electroencephalogram Data For The Classification Of Benign Partial Epilepsy Of Childhood With Centrotemporal Spikes, Jessica A. Scarborough 2017 University of San Francisco

The Acquisition And Analysis Of Electroencephalogram Data For The Classification Of Benign Partial Epilepsy Of Childhood With Centrotemporal Spikes, Jessica A. Scarborough

Master's Theses

In this thesis, I will expand upon each step in the process of acquiring and analyzing electroencephalogram (EEG) for the classification of benign childhood epilepsy with centrotemporal spikes. Despite huge advancements in the field of health informatics—natural language processing, machine learning, predictive modeling—there are significant barriers to the access of clinical data. These barriers include information blocking, privacy policy concerns, and a lack of stakeholder support. We will see that these roadblocks are all responsible for stunting biomedical research in some way, including my own experiences in acquiring the data for the second chapter of this thesis.

This ...


Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh 2017 Thomas Jefferson University

Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh

Department of Neuroscience

Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic ...


The Role Of Hsf1 Protein Regulation On Neurodegeneration, Eunhee Kim 2017 University of Tennessee Health Science Center

The Role Of Hsf1 Protein Regulation On Neurodegeneration, Eunhee Kim

Theses and Dissertations (ETD)

Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin–proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerable to toxic stress from aggregation-prone proteins such as α-synuclein. Induction of heat-shock proteins (HSPs), such as through activated heat shock transcription factor 1 (HSF1) via Hsp90 inhibition, is being investigated as a therapeutic option for proteinopathic diseases. HSF1 is a master stress-protective transcription factor which activates genes encoding protein chaperones (e.g. iHsp70) and anti-apoptotic ...


The Impact Spectrum Of Head Injuries On The Sport Of Hockey, Caleb W. Neal 2017 University of Rhode Island

The Impact Spectrum Of Head Injuries On The Sport Of Hockey, Caleb W. Neal

Senior Honors Projects

The Center for Disease Control and Prevention (CDC) estimates there are between 1.6-3.8 million sports and recreation related concussions per year. In fact there are over 4 million concussions (including non-sports related) in total each year. A concussion is defined as a serious brain injury caused by the rapid movement (linear front-to-back, side-to-side) or rotational (angular) movement of the brain inside the skull, which results in damage and disruption to the brain cell function, causing brain trauma (sports concussion library). Sports-related concussions (SRCs) are concussions that are specifically sustained during a sporting event. The sport with the highest ...


Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh 2017 University of Louisville

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system ...


Persistent Neurobehavioral Traits In A Mouse Model Of Prenatal Ethanol Exposure, Jill M. Lawrence 2017 Ursinus College

Persistent Neurobehavioral Traits In A Mouse Model Of Prenatal Ethanol Exposure, Jill M. Lawrence

Neuroscience Honors Papers

Fetal Alcohol Spectrum Disorders (FASD) effect an estimated 2% of the population, causing a range of symptoms: from craniofacial defects to inhibited cortical growth (May, et al., 2009; Murawski, et al., 2015). Impaired medial forebrain function apparent in FASD is associated with lifelong cognitive behavioral deficits, but these consequences may be avoided with early diagnosis and intervention (Streissguth, et al., 2004). Our goal is to identify early neurobehavioral abnormalities that persist into adulthood that could potentially serve as early indicators for FASD. Mouse models of prenatal ethanol exposure were developed using a voluntary drinking paradigm that introduced a sweetened ethanol ...


Serial Deletion Reveals Structural Basis And Stability For The Core Enzyme Activity Of Human Glutaminase 1 Isoforms: Relevance To Excitotoxic Neurodegeneration., Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin C. Zheng 2017 University of Nebraska Medical Center

Serial Deletion Reveals Structural Basis And Stability For The Core Enzyme Activity Of Human Glutaminase 1 Isoforms: Relevance To Excitotoxic Neurodegeneration., Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence. We have previously identified that KGA and GAC are differentially regulated during inflammatory stimulation and HIV infection. Furthermore, glutaminase 1 has ...


The Use Of Rhyme, Rhythm, And Melody As A Form Of Repetition Priming To Aid In Encoding, Storage, And Retrieval Of Semantic Memories In Alzheimer’S Patients, Faiz Plastikwala 2017 Virginia Commonwealth University

The Use Of Rhyme, Rhythm, And Melody As A Form Of Repetition Priming To Aid In Encoding, Storage, And Retrieval Of Semantic Memories In Alzheimer’S Patients, Faiz Plastikwala

Virginias Collegiate Honors Council Conference

Treating Alzheimer’s disease, especially through non-pharmaceutical means, has become increasingly important over the past few decades. I examined the use of melody, rhyme, and rhythm as encoding mechanisms to aid in the retrieval of long term semantic information by juxtaposing previous experiments in the field. Melody, rhyme, and rhythm provide an organizational structure to facilitate the encoding of information. Specifically, chunking, the grouping of smaller units into larger ‘chunks’, helps facilitate long term encoding in patients, and is the byproduct of the organizational structure of a text. A major drawback of using these devices is the loss in the ...


Receptor-Associated Protein (Rap) Models In Vivo Reelin Haploinsufficiency: Implications In Schizophrenia, Jamileh Ahmed 2017 University of South Florida

Receptor-Associated Protein (Rap) Models In Vivo Reelin Haploinsufficiency: Implications In Schizophrenia, Jamileh Ahmed

Graduate Theses and Dissertations

The “two-hit” schizophrenia hypothesis suggests genetic and environmental abnormalities interrupt early CNS function. This increases vulnerability of a “second hit” and schizophrenia onset. Chronic stress and decreased Reelin signaling are reportedly associated with schizophrenia. Heterozygous Reeler Mice (HRM) show a 50% reduction in Reelin and display major schizophrenia phenotypes. Receptor-Associated Protein (RAP) blocks ligand-association to Reelin receptor Apolipoprotein E receptor 2 (ApoER2). In this study, we sought to replicate major heterozygous reeler mouse (HRM) phenotypes using in vivo RAP studies to establish an experimental in vitro model. Using an in vitro model, we investigated the effects of chronic stress and ...


Informational Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, Ion G. Motofei, David L. Rowland 2017 Carol Davila University, St. Pantelimon Hospital

Informational Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

Many basic physiological mechanisms of sexuality were initially studied on animal subjects and conclusions regarding human subjects extrapolated afterward. These ancestral reflexes are assumed to have ascended during human evolution to the cerebral level, where cognition would intermediate (being an environmental operator) both sexual and mental processes. Accordingly, the study of human sexuality suggests an additional/ particular documentation regarding mental existence and its implication, phenomena that are not characteristic of animals.

In a previously published paper we presented ideas regarding the structural dichotomy of the mind and its subsequent implications to sexuality. In this paper we present a general perspective ...


Tau-Directed Immunotherapy For Alzheimer’S Disease, Sulana Kay Schroeder 2017 University of South Florida

Tau-Directed Immunotherapy For Alzheimer’S Disease, Sulana Kay Schroeder

Graduate Theses and Dissertations

Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 50 to 80 percent of dementia cases, and the prevalence of the disease is projected to increase significantly with time. AD is characterized by severe cognitive decline with age, ultimately requiring continued caregiving and eventually death. The pathology of AD is characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein, neuron loss, and evidence of inflammation indicated by the presence of reactive microglia and astrocytes. Frontotemporal Lobe Dementia (FTLD) is a rare form of dementia that is related to AD ...


Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez 2017 Wright State University

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Francisco J. Alvarez

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw ...


Use Of Porous Elastomer Foams To Support Long Term Three Dimensional Neuronal Cultures, Richard M. Cukelj, Elda Hegmann, Ernest Freeman, Jennifer McDonough, Robert Clements 2017 Kent State University - Kent Campus

Use Of Porous Elastomer Foams To Support Long Term Three Dimensional Neuronal Cultures, Richard M. Cukelj, Elda Hegmann, Ernest Freeman, Jennifer Mcdonough, Robert Clements

Undergraduate Research Symposium

In order to effectively study the interactions that occur between neurons found in the brain, spatially and after an extended period of time, it is necessary to have reliable, repeatable studies. This is difficult to accomplish through conventional two-dimensional cell culture techniques, but three dimensional (3D) elastomer foams satisfy these criteria. Here we present a platform to study complex neuronal networks for extended periods in vitro. Elastomer foams were constructed with pore sizes ranging from 150μm to 400μm with 40μm secondary pores which allowed human neuroblastoma cells (SH-SY5Y) to adhere and interact with the foam and be sustained for long ...


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