Transport Of Bmaa Into Neurons And Astrocytes By System XC-,
2018
Marquette University
Transport Of Bmaa Into Neurons And Astrocytes By System XC-, Rebecca Albano, Doug Lobner
Biomedical Sciences Faculty Research and Publications
The study of the mechanism of β-N-methylamino-l-alanine (BMAA) neurotoxicity originally focused on its effects at the N-methyl-d-aspartate (NMDA) receptor. In recent years, it has become clear that its mechanism of action is more complicated. First, there are certain cell types, such as motor neurons and cholinergic neurons, where the dominate mechanism of toxicity is through action at AMPA receptors. Second, even in cortical neurons where the primary mechanism of toxicity appears to be activation of NMDA receptors, there are other mechanisms involved. We found that along with NMDA receptors, activation of mGLuR5 receptors and effects on the …
What Does The Fos Say? Using Fos-Based Approaches To Understand The Contribution Of Stress To Substance Use Disorders,
2018
Marquette University
What Does The Fos Say? Using Fos-Based Approaches To Understand The Contribution Of Stress To Substance Use Disorders, Jayme R. Mcreynolds, John P. Christianson, Jordan M. Blacktop, John Mantsch
Biomedical Sciences Faculty Research and Publications
Despite extensive research efforts, drug addiction persists as a largely unmet medical need. Perhaps the biggest challenge for treating addiction is the high rate of recidivism. While many factors can promote relapse in abstinent drug users, the contribution of stress is particularly problematic, as stress is uncontrollable and pervasive in the lives of those struggling with addiction. Thus, understanding the neurocircuitry that underlies the influence of stress on drug seeking is critical for guiding treatment. Preclinical research aimed at defining this neurocircuitry has, in part, relied upon the use of experimental approaches that allow visualization of cellular and circuit activity …
17Β-Estradiol Potentiates The Reinstatement Of Cocaine Seeking In Female Rats: Role Of The Prelimbic Prefrontal Cortex And Cannabinoid Type-1 Receptors,
2018
Marquette University
17Β-Estradiol Potentiates The Reinstatement Of Cocaine Seeking In Female Rats: Role Of The Prelimbic Prefrontal Cortex And Cannabinoid Type-1 Receptors, Elizabeth M. Doncheck, Luke A. Urbanik, Margot C. Debaker, Laura M. Barron, Gage T. Liddiard, Jennifer J. Tuscher, Karyn M. Frick, Cecilia J. Hillard, John Mantsch
Biomedical Sciences Faculty Research and Publications
Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose …
Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke,
2018
University of Kentucky
Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix
Neuroscience Faculty Publications
BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.
OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.
METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …
Disturbance Of Redox Homeostasis In Down Syndrome: Role Of Iron Dysmetabolism,
2018
Sapienza University of Rome, Italy
Disturbance Of Redox Homeostasis In Down Syndrome: Role Of Iron Dysmetabolism, Eugenio Barone, Andrea Arena, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi
Sanders-Brown Center on Aging Faculty Publications
Down syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD). The neuropathology of DS has several common features with AD including alteration of redox homeostasis, mitochondrial deficits, and inflammation among others. Interestingly, some of the genes encoded by chromosome 21 are responsible of increased oxidative stress (OS) conditions that are further exacerbated by decreased antioxidant defense. Previous studies from our groups showed that accumulation of oxidative damage is an early event in DS neurodegeneration and that oxidative modifications of selected proteins affects the integrity …
Microrna Expression Patterns In Human Anterior Cingulate And Motor Cortex: A Study Of Dementia With Lewy Bodies Cases And Controls,
2018
University of Kentucky
Microrna Expression Patterns In Human Anterior Cingulate And Motor Cortex: A Study Of Dementia With Lewy Bodies Cases And Controls, Peter T. Nelson, Wang-Xia Wang, Sarah A. Janse, Katherine L. Thompson
Sanders-Brown Center on Aging Faculty Publications
Overview
MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB).
Methods
RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals. RNA was profiled using Exiqon miRNA microarrays. Quantitative PCR for post-hoc replication was performed on separate cases (n=6 controls) and included RNA isolated from gray matter of MO, AC, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions.
Results
The miRNA expression patterns differed substantially according to …
Can Nox1 Activity Initiate Parkinson's-Like Pathology In An Enteroendocrine Cell Line?,
2018
University of Central Florida
Can Nox1 Activity Initiate Parkinson's-Like Pathology In An Enteroendocrine Cell Line?, Evan Adler
Honors Undergraduate Theses
Increased attention has been given to the gut lately in a number of conditions, from maintaining health via the use of probiotics to treating Autism Spectrum Disorder. Parkinson's Disease has a history with the gut starting with the Braak hypothesis, in which eminent researcher Heiko Braak observed that the spread of Parkinson's (PD) seemed to occur along either olfactory or enteric neurons prior to reaching the substantia nigra in the midbrain, where the classical disease symptoms become evident. Though this finding was largely ignored at the time, the possibility of a gut origin for PD has received interest lately as …
Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets,
2018
University of Kentucky
Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets, Eseosa T. Ighodaro
Theses and Dissertations--Neuroscience
Cerebrovascular disease is a major cause of dementia in elderly individuals, especially Black/African Americans. Within my dissertation, we focused on two vascular morphologies that affect small vessels: brain arteriolosclerosis (B-ASC) and multi-vascular profiles (MVPs). B-ASC is characterized by degenerative thickening of the wall of brain arterioles. The risk factors, cognitive sequelae, and co-pathologies of B-ASC are not fully understood. To address this, we used multimodal data from the National Alzheimer’s Coordinating Center, Alzheimer’s Disease Neuroimaging Initiative, and brain-banked tissue samples from the University of Kentucky Alzheimer’s Disease Center (UK-ADC) brain repository. We analyzed two age at death groups separately: < 80 years and ≥ 80 years. Hypertension was a risk factor in the < 80 years at death group. In addition, an ABCC9 …
Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke,
2018
University of Kentucky
Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron
Theses and Dissertations--Neuroscience
Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …
Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment,
2018
University of Kentucky
Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang
Theses and Dissertations--Pharmacy
Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …
Gene Regulation In The Hypothalamic-Pituitary-Gonadal Axis Of The Green Anole Lizard (Anolis Carolinensis).,
2018
Minnesota State University, Mankato
Gene Regulation In The Hypothalamic-Pituitary-Gonadal Axis Of The Green Anole Lizard (Anolis Carolinensis)., Joshua N. Peters
All Graduate Theses, Dissertations, and Other Capstone Projects
Studies examining the hypothalamic-pituitary-gonad axis (HPG) in Anolis carolinensis provide insight into the regulation of this axis under extremely different reproductive conditions. Molecular studies indicate that kisspeptin proteins, transcribed from kiss1 and kiss2 genes, are produced in the hypothalamus where they bind G protein-coupled receptor 54 (GPR54), activating the HPG axis. Gonadotropin inhibitory hormone (GnIH) and its receptors, G protein-coupled receptor 147 and 74 (GPR147 and GPR74), down regulate HPG axis function. In this experiment we examined HPG axis gene expression in the green anole lizard (Anolis carolinensis), a seasonally breeding species with higher steroid hormone levels in the breeding …
Under The Influence: An Interdisciplinary Approach To Psychedelics,
2018
Rollins College
Under The Influence: An Interdisciplinary Approach To Psychedelics, Jody Roun
Master of Liberal Studies Theses
The following research will outline the effects of psychedelics from an interdisciplinary approach, which is to say that I will explore the neuroscience behind psychedelic drugs and how it relates to creativity, as a primary focus, while examining the role of additional points included along the way. The goal of this research, is to gain a deeper understanding of psychedelics and truly decipher what it means to be under the influence, as the most important goal of this human existence is to achieve understanding. The aforementioned is a point that great minds like Albert Einstein and Humphry Osmond impressed on …
Down Syndrome, Beta-Amyloid And Neuroimaging,
2018
University of Kentucky
Down Syndrome, Beta-Amyloid And Neuroimaging, Elizabeth Head, Alex M. Helman, David K. Powell, Frederick A. Schmitt
Sanders-Brown Center on Aging Faculty Publications
This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we …
Characteristics Of Neuropathic Pain In Individuals With Chronic Spinal Cord Injury,
2018
Neurosciences
Characteristics Of Neuropathic Pain In Individuals With Chronic Spinal Cord Injury, Hossein Majedi, Mahdi Safdarian, Marzieh Hajiaghababaei, Alexander R. Vaccaro, Vafa Rahimi-Movaghar
Neurosciences
Objectives: To present the characteristics of neuropathic pain in individuals with chronic spinal cord injury (SCI). Methods: We recruited all individuals with chronic SCI referred to the Brain and Spine Injury Research center with a diagnosis of neuropathic pain from April 2013 to September 2015 into this historical cohort study. Results: Forty individuals with chronic SCI-induced neuropathic pain entered this study with a mean age of 43.67±13.12 years and a majority of who were male (n=30, 75%). Motor vehicle collision (n=25, 62.5%) and fall (n=7, 17.5%) were the most common causes of SCI in our participants. There were 13 (32.5%) …
Investigating The Relationship Between Sulcogyral Patterns And Structural And Functional Connectivity Metrics In The Orbitofrontal Cortex,
2018
Bucknell University
Investigating The Relationship Between Sulcogyral Patterns And Structural And Functional Connectivity Metrics In The Orbitofrontal Cortex, Bethany M. Blass
Honors Theses
Located within the frontal lobe, the human orbitofrontal cortex (OFC) is widely known for its roles in sensory integration, emotion processing, decision-making, and goal-directed behaviors. Atypical structural organization of the OFC may explain atypical social or motivational behaviors displayed by individuals with brain disorders, such as bipolar disorder patients (BP).
The human brain can be imaged using magnetic resonance imaging (MRI) to reveal interesting aspects of the underlying brain architecture. This brain is composed of different tissue types, including gray and white matter, as well as various morphological features, including sulci & gyri. Within the OFC, the sulci can be …
The Opiod Epidemic: Clinical Dental Update,
2018
Marquette University
The Opiod Epidemic: Clinical Dental Update, Matthew Hearing
Biomedical Sciences Faculty Research and Publications
No abstract provided.
On The Future Of Antidepressant Treatments: Targeting Neurotrophic Factors And Plasticity,
2018
University of Mississippi
On The Future Of Antidepressant Treatments: Targeting Neurotrophic Factors And Plasticity, Stephen W. White
Electronic Theses and Dissertations
For 60-plus years the explanatory model for Major Depressive Disorder (MDD) has been the monoamine theory, which states that low levels of monoamine neurotransmitters or alterations in their post-synaptic receptors are responsible for depressive symptoms. Drugs designed to elevate synaptic monoamine levels have remained the first line of pharmacotherapy prescribed by clinicians for MDD patients. However, these drugs have shortcomings. Despite evidence that current antidepressants elevate synaptic monoamine levels within hours of administration, these drugs require four to six weeks of daily administration before symptom relief appears. Furthermore, approximately half of patients taking typical antidepressants never achieve full symptom relief. …
Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits,
2018
University of Florida
Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth
Faculty & Staff Scholarship
Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α’ catalytic subunits and two identical cone-specific PDE6γ’ inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α’ subunits. Both rod and …
Sphingomyelin And Gm1 Influence Huntingtin Binding To, Disruption Of, And Aggregation On Lipid Membranes,
2018
West Virginia University
Sphingomyelin And Gm1 Influence Huntingtin Binding To, Disruption Of, And Aggregation On Lipid Membranes, Maxmore Chaibva, Xiang Gao, Pranav Jain, Warren A. Campbell, Shelli L. Frey, Justin Legleiter
Faculty & Staff Scholarship
Huntington disease (HD) is an inherited neurodegenerative disease caused by the expansion beyond a critical threshold of a polyglutamine (polyQ) tract near the N- terminus of the huntingtin (htt) protein. Expanded polyQ promotes the formation of a variety of oligomeric and fibrillar aggregates of htt that accumulate into the hallmark proteina- ceous inclusion bodies associated with HD. htt is also highly associated with numerous cellular and subcellular membranes that contain a variety of lipids. As lipid homeostasis and metabolism abnormalities are observed in HD patients, we investigated how varying both the sphingomyelin (SM) and ganglioside (GM1) contents modifies the interactions …
The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency,
2018
Wayne State University
The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome
Wayne State University Dissertations
The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …
