Neurosciences Commons^™

Exercise-Induced Neuroprotection In A Hemiparkinsonian 6-Hydroxydopamine Rat Model, Merrill Russen Landers

UNLV Theses, Dissertations, Professional Papers, and Capstones

Outside of finding a cure, one of the preeminent goals of research in Parkinson's disease (PD) is finding a neuroprotective treatment that when applied prior to the onset of the disease will decrease the risk and severity of the subsequent disease. One such treatment that has potential as a neuroprotective agent in PD is exercise. Several studies have found forced exercise to be protective of Parkinson's disease in adult rodent models; however, few of these studies have used a design wherein voluntary exercise was evaluated. Moreover, no study has used a true neuroprotective design in which exercise was applied prior …

Effects Of Hyperthermia On Photochemical Internalization-Mediated Delivery Of Bleomycin, Christina Schlazer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment protocols for high-grade gliomas, such as glioblastoma multiforme (GBM), are highly ineffective due to their inability to eradicate infiltrating tumor cells. Improvements in overall survival are likely to be realized only with the development of more effective localized therapies capable of eradicating tumor cells in the surgical resection margin and beyond. Photochemical internalization (PCI) is a localized light-based therapeutic modality that enhances the efficacy of therapeutic macromolecules including chemotherapeutic agents such as bleomycin. A number of studies have shown that this photodynamic therapy (PDT) - based modality may prove effective in the treatment of high-grade gliomas.

Three-dimensional multicell …

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

Ensembles Of Human Mtl Neurons "Jump Back In Time" In Response To A Repeated Stimulus, M. W. Howard, Indre Viskontas, K. H. Shankar, I. Fried

Psychology

Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as ‘‘mental time travel’’ in which the rememberer ‘‘jumps back in time.’’ The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus …

Increasing Parity Is Associated With Cumulative Effects On Memory, Laura M. Glynn

Psychology Faculty Articles and Research

BACKGROUND: The purpose of this investigation was to determine if reproductive experience is associated with cumulative effects on human memory performance during pregnancy and if these effects persist into the postpartum period.

METHODS: Verbal recall memory performance was assessed in 254 women four times during pregnancy and at 3 months postpartum. The relation between parity and memory function was evaluated with hierarchical linear modeling and analysis of covariance (ANCOVA).

RESULTS: The data indicate that the previously documented adverse effects of pregnancy on memory performance are compounded with successive pregnancies. During gestation and postpartum, multiparity was associated with poorer memory function, …

Uncertain Progress On The Fuzzy Boundaries Of Alzheimer's Disease: Reading Between The Guidelines, Peter J. Whitehouse

Faculty Scholarship

No abstract provided.

Brain Activation And Connectivity In Non-Disabled Multiple Sclerosis Patients, Rene A. Colorado

Dissertations and Theses (Open Access)

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. There is no cure for MS and current therapies have limited efficacy. While the majority of individuals with MS develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). The current studies combined functional MRI and diffusion tensor imaging (DTI) to elucidate brain mechanisms associated with lack of clinical disability in patients with MS. Recent evidence has implicated cortical reorganization as a mechanism to limit the clinical manifestation of …

Prevalence Of Premature Ovarian Failure In Women With Tuberous Sclerosis, Emily Gabitzsch

Dissertations and Theses (Open Access)

Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor disorder characterized by hamartomas, or benign growths, in various organ systems. Inactivating mutations in either the TSC1 or the TSC2 gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of Tsc1 or Tsc2 showed accelerated ovarian follicle activation and subsequent premature follicular depletion, consistent with the human condition premature ovarian failure (POF). POF is defined in women as the cessation of menses before the age of 40 …

Optimality In Neural Adaptation, Adrienne Fairhall

Systems Science Friday Noon Seminar Series

Nervous systems tune themselves to the statistical structure of the stimuli they encounter. This sensitivity to statistics appears in phenomena ranging over many timescales, from the adaptation of vision to a rapid change in light level to the loss of ability to distinguish the sounds of non-native languages. While multiple neural mechanisms contribute to this on-line learning of stimulus distributions, we show that the intrinsic nonlinearities of single neurons provide them with the ability to represent time-varying stimuli optimally. While such sensitivity to stimulus statistics does not require learning, slower timescales of adaptation are consistent with optimal inference of statistical …

Patterns Of Microrna Expression In Normal And Early Alzheimer's Disease Human Temporal Cortex: White Matter Versus Gray Matter, Wang-Xia Wang, Qingwei Huang, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM miRNA repertoires across a range of Alzheimer's disease (AD) pathology. RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval < 4 h). miRNA profiling experiments were performed using state-of-the-art Exiqon^© LNA-microarrays. A subset of miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional miRNAs according to Northern blot analyses. Some well-characterized miRNAs were substantially enriched in WM …

Δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 And Peptide Transporter 2*2 Haplotype May Differentially Mediate Lead Exposure In Male Children, Christina Sobin, Natali Parisi, Tanner Schaub, Marisela Gutierrez, Alma Ortega

Selected Works Temporary Series

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, d-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and/or peptide transporter 2*2 haplotype (hPEPT2*2) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Research outputs 2011

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

The Effect Of Spiritualism On The Neuropsychological Function Of Memory, Carla Farcello

McNair Poster Presentations

The amount of physiological-neurological research performed over the past few years has dramatically increased due to our ability to view the structure and function of the brain in living human beings. The use of imaging tools has resulted in huge strides forward in unlocking some of the mysteries of the 3 pound universe-the human brain. One of the more unique neural processes being recently addressed is the affect of belief and spiritualism-the sense of being connected to something larger than oneself-on the human brain. This study hypothesized that better memory will be documented among the experimental group who report being …

Getting To Know You: Key Clinical Concepts In Relationship-Based Interventions And Neurobehavioral Observations With Young Infants, Yvette Blanchard

All PTHMS Faculty Publications

The newborn infant is a social organism, pre-disposed to interact with his caregiver and able to elicit the kind of caregiving necessary for successful adaptation. The earliest developmental task of the newborn is to organize behavior to be able to play an active role in influencing the caregiving environment and eliciting the kind of support needed for development. This task is accomplished through the attainment of self-regulation or balanced neurobehavioral functioning of the infant's autonomic, motor, state, and responsivity behavioral dimensions as described by Als.

Donepezil And Galanin Interactions In An Animal Model Of Alzheimer’S Disease, Jonathan J. Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by a progressive loss of cognitive function. One of the neurobiological hallmarks of AD is a progressive loss of cholinergic neurons and a decrease in the amount of acetylcholine in the brain. Pharmacological therapies have targeted the cholinergic system, specifically first-line, palliative treatment using acetylcholinesterase (AChE) inhibitors, such as donepezil. Donepezil has been shown to increase cholinergic tone and ameliorate some of the cognitive deficits in AD patients. Galanin, a neuropeptide that inhibits the evoked release of several neurotransmitters including acetylcholine as well as modulates seveal intracellular cascades, is overexpressed in AD …

Dysregulation Of The Mitogen Granulin In Human Cancer Through The Mir-15/107 Microrna Gene Group, Wang-Xia Wang, Natasha Kyprianou, Xiaowei Wang, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Granulin (GRN) is a potent mitogen and growth factor implicated in many human cancers, but its regulation is poorly understood. Recent findings indicate that GRN is regulated strongly by the microRNA miR-107, which functionally overlaps with miR-15, miR-16, and miR-195 due to a common 5′ sequence critical for target specificity. In this study, we queried whether miR-107 and paralogs regulated GRN in human cancers. In cultured cells, anti-argonaute RNA coimmunoprecipitation with downstream microarray analyses indicates that GRN mRNA is directly targeted by numerous miR-15/107 miRNAs. We further tested this association in human tumors. MiR-15 and miR-16 are known to be …

Neural Coding And Decoding, Alexander Dimitrov

Systems Science Friday Noon Seminar Series

Methods based on Rate Distortion theory have been successfully used to cluster stimuli and neural responses in order to study neural codes at a level of detail supported by the amount of available data. They approximate the joint stimulus-response distribution by quantizing paired stimulus-response observations into smaller reproductions of the stimulus and response spaces. An optimal quantization is found by maximizing an information-theoretic cost function subject to both equality and inequality constraints, in hundreds to thousands of dimensions. This analytical approach has several advantages over other current approaches:

• it yields the most informative approximation of the encoding scheme given the …

Pontine Haemorrhage Due To Chondrosarcoma Of The Skull Base, Maliha Iqbal Jumani, Roomasa Channa, Sayed Nabeel Zafar, Ather Enam

Section of Neurosurgery

A young adult presented with acute weakness of right side of body and slurring of speech. An initial brain CT scan showed a pontine haemorrhage, however MRI done a few days later revealed a mass in the left parapharyngeal space. Histopathology of the mass revealed that it was a chondrosarcoma. Subsequently the patient was initially treated with chemotherapy and radiotherapy and later surgery. Skull base chondrosarcomabe is to be included in the differentials of a young patient presenting with signs consistent with pontine haemorrhage.

The Mir-15/107 Group Of Microrna Genes: Evolutionary Biology, Cellular Functions, And Roles In Human Diseases, John R. Finnerty, Wang-Xia Wang, Sébastien S. Hébert, Bernard R. Wilfred, Guogen Mao, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

Individual Micrornas (Mirnas) Display Distinct Mrna Targeting "Rules", Wang-Xia Wang, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using …

Development Of A Functional Mri Olfactory Protocol, Jeremy Mangum

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many people can spend a few days with an acute form of sinusitis, a stuffy nose, or sinus congestion that inhibits their ability to smell, but there are fourteen million Americans over the age of fifty that suffer from some form of chronic olfactory dysfunction. Some neurological disorders such as Parkinson's disease and Alzheimer's disease have demonstrated that olfactory dysfunction is a frequent and early sign. While these diseases have no known cure, there are medicines that exist to slow the progression of such debilitating illnesses. By identifying such diseases in their early stages, we can improve the quality of …

Molecular Cross Talk Between Misfolded Proteins In Animal Models Of Alzheimer's And Prion Diseases, Rodrigo Morales, Lisbell D Estrada, Rodrigo Diaz-Espinoza, Diego Morales-Scheihing, Maria C Jara, Joaquin Castilla, Claudio Soto

Faculty, Staff and Student Publications

The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration …

Sharing Neurological Expertise: Development Of A High Risk Obstetrical Course, Maureen T. Smith Msn, Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Anti-Argonaute Rip-Chip Shows That Mirna Transfections Alter Global Patterns Of Mrna Recruitment To Microribonucleoprotein Complexes, Wang-Xia Wang, Bernard R. Wilfred, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify …

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.

Safe Emergency Management Of Acute Ischemic Stroke: An Academic Community Hospital Decade Experience, John Castaldo, Richard S. Mackenzie Md, Peter J. Barbour Md, Lorraine Spikol, Yevgeniy Isayev, Yuebing Li Phd, Gary Clauser Md, John Margraf Md, Glenn Mackin Md, Faan, Facp, David Richardson, Gavin C. Barr, Jr. Md, Donna Jenny, Susan Nevada, Claranne Mathiesen

Department of Emergency Medicine

No abstract provided.

Disclosure Of Apoe Genotype For Risk Of Alzheimer's Disease, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

BACKGROUND: The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. METHODS: We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. RESULTS: There were no significant differences between the …

Treatment Options For Neuropathic Pain, Sara Akre

Honors Program Theses

Neuropathic pain is caused by injury to or disease of the nervous system. It affects many people around the world and is a symptom of several diseases. In the United States, it is estimated that up to 3% of Americans have neuropathic pain, which costs the healthcare system $40 billion annually (Gilron et al. 2006). It is, unfortunately, difficult to ameliorate or eliminate due to the complexity of the nervous system and its plasticity and is, therefore, a chronic condition. Health care professionals continually struggle to treat patients' pain and, since tolerance to painkillers is easily built up, this often …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …