Neurosciences Commons^™

Bitc Sensitizes Pancreatic Adenocarcinomas To Trail-Induced Apoptosis, Christina A. Wicker, Ravi P. Sahu, Kashmira Kulkarni-Datar, Sanjay K. Srivastava, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetables and a cell cycle …

Drug-Induced Plasticity Contributing To Heightened Relapse Susceptibility: Neurochemical Changes And Augmented Reinstatement In High-Intake Rats, Aric Madayag, Kristen S. Kau, Doug Lobner, John R. Mantsch, Samantha Wisniewski, David A. Baker

Biomedical Sciences Faculty Research and Publications

A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats …

Explorations In Homeoviscous Adaptation And Mass Spectral Analysis Of Membrane Lipids, Michael Douglas Timmons

University of Kentucky Doctoral Dissertations

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment.

The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass …

Studies Of The Effects Of Dopamine Neuron Stimulating Peptides In Rodent Models Of Normal And Dysfunctional Dopaminergic Systems, Joshua Lee Fuqua

University of Kentucky Doctoral Dissertations

A theoretical post-translational processing model of the proprotein form of glial cell line-derived neurotrophic factor (GDNF) likely produces three biologically active peptides. The three prospective peptides formed are 5, 11, and 17 amino acid peptides, entitled dopamine neuron stimulating peptide -5 (DNSP-5), -11 (DNSP-11), and -17 (DNSP-17), respectively. The DNSPs were hypothesized to increase dopaminergic neuron function because of their relationship to GDNF: a molecule with established neurotrophic actions on dopaminergic neurons. The DNSPs have the potential to provide a therapeutic molecule similar to GDNF, but with increased ease of delivery and improved bioavailability.

Neurochemical effects of DNSPs were examined …

A New Nonlinear Classifier With A Penalized Signed Fuzzy Measure Using Effective Genetic Algorithm, Julia Hua Fang, Maria L. Rizzo, Honggang Wang, Kimberly A. Espy, Zhenyuan Wang

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

This paper proposes a new nonlinear classifier based on a generalized Choquet integral with signed fuzzy measures to enhance the classification accuracy and power by capturing all possible interactions among two or more attributes. This generalized approach was developed to address unsolved Choquet-integral classification issues such as allowing for flexible location of projection lines in n-dimensional space, automatic search for the least misclassification rate based on Choquet distance, and penalty on misclassified points. A special genetic algorithm is designed to implement this classification optimization with fast convergence. Both the numerical experiment and empirical case studies show that this generalized …

Regulation Of Neuronal Excitability: New Mechanisms For Slow Afterhyperpolarization Activation And Modulation, Claudio Alberto Villalobos

Wayne State University Dissertations

One of the most characteristic features of pyramidal cells in the prefrontal cortex (PFC) is that they present a slow afterhyperpolarizing current (I_sAHP) that plays a critical role in the regulation of neuronal excitability. This current is modulated by receptors acting via GΑ_q/11 G proteins, thus it is thought that neurotransmitters regulate neuronal excitability through the inhibition of this current. I_sAHP is known to be mediated by calcium-activated potassium channels, however, neither the identity of the channel underlying this current nor its mechanism of activation are yet well understood. Recent reports have questioned a direct role …

Age- And Sex-Associated Changes In Mrna Expression Of Neurodegenerative Disorder-Related Molecules In The Hippocampus And Cerebellum Of Rat Brain, Srinivasarao Thulluri

Theses, Dissertations and Capstones

Age-associated oxidative stress is involved in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, and sex-associated differences may also affect the risk for these neurodegenerative diseases. We compared the effects of aging and sex on the mRNA expression of five molecules that are closely related to oxidative stress, along with Alzheimer’s and Parkinson’s diseases in the hippocampus of both male and female Fischer 344xBrown Norway (F344BN) rats. The reverse transcription polymerase chain reaction was used to determine the mRNA expression level of superoxide dismutase 2 (SOD2), heme oxygenase 1 (HO1), amyloid precursor protein (APP), -site APP-cleaving enzyme 1 (BACE1), and …

Electrospun Nanofibers For Neural Tissue Engineering, Jingwei Xie, Matthew R. Macewan, Andrea G. Schwartz, Younan Xia

MIIR Faculty Research

Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment for the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Activation Of Peroxisome Proliferator-Activated Receptor G In Brain Inhibits Inflammatory Pain, Dorsal Horn Expression Of Fos, And Local Edema, Jenny Morgenweck, Omar D. Abdel-Aleem, Katelyn C. Mcnamara, Renee R. Donahue, M Z. Badr, Bradley K. Taylor

Renee R. Donahue

Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumablybyacting at peroxisome proliferator-activated receptor g (PPARg) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARg actions, we postulated that brain PPARg modulates peripheral edema and the processing of inflammatory pain signals in the dorsal horn of the spinal cord. To test this in the plantar carrageenan model of inflammatory pain, we measured paw edema, heat hyperalgesia, and dorsal horn expression of the immediate-early gene c-fos after intracerebroventricular (ICV) administration of PPARg ligands or vehicle. We found that ICV rosiglitazone …

Autotaxin: A Regulator Of Oligodendrocyte Differentiation, Larra Yuelling

Theses and Dissertations

In order for oligodendrocyte progenitor cells (OPCs) to differentiate into fully mature, myelinating oligodendrocytes, they must be specified at the correct times and undergo coordinated changes in both gene expression and morphology. As oligodendrocytes differentiate, they transition from a bipolar morphology into a morphology characterized by a complex network of multiple processes, which will eventually generate membranous structures necessary for myelination of axonal segments. As changes are observed in cellular morphology, oligodendrocytes also undergo changes in their gene expression profile and express genes necessary for both early and later stages of development such as olig1 and myelin basic protein (mbp), …

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …

Comparison Of Affective Analgesia And Conditioned Place Preference Following Cholinergic Activation Of, Elena Schifirnet

Wayne State University Dissertations

Activation of the dopaminergic mesolimbic reward circuitry that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress affective reactions to noxious stimuli (affective analgesia, AA). VTA dopamine neurons are activated via cholinergic inputs, and we have observed that microinjections of the acetylcholine agonist carbachol suppressed vocalizations of rats that occur following administration of brief (1 sec) tail-shocks (vocalization afterdischarges = VAD). VADs are a validated rodent model of pain affect. In addition, the capacity of carbachol to support reinforcement appears to be regionally dependent within VTA. Ikemoto and Wise (2002) reported that carbachol was self-administered in the …

The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger

Theses and Dissertations

We study the activity-dependent refinement of sensory systems by using the mouse retinogeniculate system as a model. Spontaneous retinal waves lead to robust excitatory post-synaptic activity in developing relay cells in the dorsal lateral geniculate nucleus (dLGN) of the thalamus and are reportedly needed to help guide the segregation of retinal inputs into eye-specific domains as well as for the pruning of extraneous retinal inputs onto single dLGN relay cells. The composition of retinally evoked post-synaptic activity activated by these retinal waves in dLGN is largely unknown, but based on our in vitro recordings, such activity seems well suited to …

Expanding The Treatment Window Raising The Bar For Patient Safety, Claranne Mathiesen Rn, Msn, Cnrn

Patient Care Services / Nursing

No abstract provided.

In Vitro Application Of Gold Nanoprobes In Live Neurons For Phenotypical Classification, Connectivity Assessment, And Electrophysiological Recording, Karl C. Mendoza

Dissertations, Theses, and Masters Projects

No abstract provided.

Lifting Without Seeing: The Role Of Vision In Perceiving And Acting Upon The Size Weight Illusion, Gavin Buckingham, Melvyn Goodale

Gavin Buckingham

BACKGROUND: Our expectations of an object's heaviness not only drive our fingertip forces, but also our perception of heaviness. This effect is highlighted by the classic size-weight illusion (SWI), where different-sized objects of identical mass feel different weights. Here, we examined whether these expectations are sufficient to induce the SWI in a single wooden cube when lifted without visual feedback, by varying the size of the object seen prior to the lift.

METHODOLOGY/PRINCIPAL FINDINGS: Participants, who believed that they were lifting the same object that they had just seen, reported that the weight of the single, standard-sized cube that they …

The Relation Of Aerobic Fitness To Neuroelectric Indices Of Cognitive And Motor Task Preparation, Jason Themanson, Keita Kamijo, Kevin O'Leary, Matthew Pontifex, Charles Hillman

Jason R. Themanson, Ph.D

The relation of aerobic fitness to task preparation was examined in a sample of young adults separated into higher- and lower-fit groups according to their maximal oxygen consumption. Participants performed a modified Sternberg working memory task under speed and accuracy instructions while measures of task performance and contingent negative variation (CNV) were collected. Analyses revealed no significant fitness differences between groups on task performance measures. However, frontal CNVamplitude was significantly larger for lower-fit participants compared to higher-fit participants during the speed instructions, an effect not found for the accuracy instructions. These results suggest that lower-fit individuals may rely to a …