Life Sciences Commons^™

Rescuing Age-Related Proteolysis Deficits With Methylene Blue, Shane E. Pullins

Theses and Dissertations

The average lifespan is constantly increasing with the advent of new medical techniques, and age-related cognitive decline is becoming a prevalent societal issue. Even during healthy aging, humans and rats exhibit progressive deficits in episodic/declarative memory. In laboratory rats, age-related memory impairment can be assessed with trace fear conditioning (TFC). Recent research implicates ubiquitin proteasome system-mediated protein degradation in the synaptic plasticity supporting memory formation and retrieval. In rats, aging leads to decreased basal proteolytic activity in brain structures known to support the acquisition and retrieval of trace fear memories, and our preliminary data suggests activity-dependent proteasome activity declines in …

The Impact Of Delay On Retrieval Success In The Parietal Memory Network, Nathan Anderson

Arts & Sciences Electronic Theses and Dissertations

Recent work has identified a Parietal Memory Network (PMN), which exhibits regular patterns of activation during memory encoding and retrieval. Among these characteristic patterns, this network displays a strong “retrieval success” effect, showing greater activation for correctlyremembered studied items (hits) compared to correctly-rejected novel items (CRs). To date, most relevant studies have used short retention intervals. Here, we ask if the retrieval success effect seen in the PMN would remain consistent over a delay. Twenty participants underwent fMRI while encoding and recognizing scenes. Greater activity for hits than for correctly-rejected lures within PMN regions was observed after a short delay …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Acute Treatment With Doxorubicin Affects Glutamate Neurotransmission In The Mouse Frontal Cortex And Hippocampus, Theresa Currier Thomas, Joshua A. Beitchman, Francois Pomerleau, Teresa Noel, Paiboon Jungsuwadee, D. Allan Butterfield, Daret K. St. Clair, Mary Vore, Greg A. Gerhardt

Spinal Cord and Brain Injury Research Center Faculty Publications

Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25 mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) …

Combined Mnemonic Strategy Training And High-Definition Transcranial Direct Current Stimulation For Memory Deficits In Mild Cognitive Impairment, Benjamin M. Hampstead, Krishnankutty Sathian, Marom Bikson, Anthony Y. Stringer

Publications and Research

Introduction: Memory deficits characterize Alzheimer’s dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level–dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS).

Methods: This protocol describes …

Mechanisms Involved In The Assessment Of Cumulative Long-Term Familiarity Of Object Concepts: An Erp Study, Haopei Yang

Electronic Thesis and Dissertation Repository

We investigated the sensitivity of ERP components implicated in recognition memory to degree of experimentally controlled and lifetime cumulative exposures during explicit memory judgements. A parietally distributed ERP component spanning both the FN400/N400 and the LPC time windows tracked both types of judgements. This effect appears to be an LPC effect with an early onset, and differs from previously reported effects of repetition linked to implicit memory. Based on recent evidence, we interpreted it as response-related evidence accumulation processes that are in line with both single-process models and continuous dual-process models. We also observed more positive ERPs in the left …

Role Of Exercise And Stress In Memory And Learning Of The Hippocampus, Paul Baker, Jeff Edwards

Journal of Undergraduate Research

Some of the most devastating diseases today are diseases of the mind. Common side effects of Alzheimer’s disease are dementia and memory loss and more than 44 million people suffer from the disease worldwide [1]. Other mental diseases such as Parkinson’s also have a dramatic impact on the memory and learning pathways. Understanding the mechanism involved with memory and learning will bring science that much closer to finding a permanent cure to these devastating diseases.

Species Differences In Egocentric Navigation: The Effect Of Burrowing Ecology On A Spatial Cognitive Trait In Mice, Jason N. Bruck, Noah A. Allen, Kelsey E. Brass, Brian A. Horn, Polly Campbell

Faculty Publications

© 2017 The Association for the Study of Animal Behaviour Efficient navigation is a critical component of fitness for most animals. While most species use a combination of allocentric (external) and egocentric (internal) cues to navigate through their environment, subterranean environments present a unique challenge in that visually mediated allocentric cues are unavailable. The relationship between egocentric spatial cognition and species differences in ecology is surprisingly understudied. We used a maze-learning task to test for differences in egocentric navigation between two closely related species of mice, the eastern house mouse, Mus musculus musculus, and the mound-building mouse, Mus spicilegus. The …

Characterization And Reversal Of Doxorubicin-Mediated Changes In Sensory Neurons, Brittany L. Coughlin

Dissertations & Theses (Open Access)

Chemotherapeutic agents impair memory in humans as well as in animal models. Such memory impairments can be persistent, lasting years after exposure to chemotherapy. Doxorubicin (DOX), a common chemotherapeutic agent, has been associated with memory impairments in humans and induces memory deficits in rodent models. DOX also impairs serotonin (5-HT)-induced long-term synaptic facilitation (LTF) in Aplysia sensorimotor co-cultures, a cellular analog of long-term memory formation. In addition, DOX leads to dynamic activation of extracellular signal-regulated kinase (ERK), consisting of an immediate and a delayed phase of activation, and to transient activation of p38 mitogen-activated protein kinase (p38 MAPK) in Aplysia …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …

Neuroimaging Biomarkers Of Caloric Restriction On Brain Metabolic And Vascular Functions, Ai-Ling Lin, Ishita Parikh, Jared D. Hoffman, David Ma

Sanders-Brown Center on Aging Faculty Publications

Purpose of Review

Non-invasive neuroimaging methods have been developed as powerful tools for identifying in vivo brain functions for studies in humans and animals. Here, we review the imaging biomarkers that are being used to determine the changes within brain metabolic and vascular functions induced by caloric restriction (CR) and their potential usefulness for future studies with dietary interventions in humans.

Recent Findings

CR causes an early shift in brain metabolism of glucose to ketone bodies and enhances ATP production, neuronal activity, and cerebral blood flow (CBF). With age, CR preserves mitochondrial activity, neurotransmission, CBF, and spatial memory. CR also …

Hippocampal Contribution To Context Encoding Across Development Is Disrupted Following Early-Life Adversity, Hilary K. Lambert, Margaret A. Sheridan, Kelly A. Sambrook, Maya L. Rosen, Mary K. Askren, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children (N = 60; 8–19 years, 24 exposed to interpersonal violence) completed acon text encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates …

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Behavioral Science Faculty Publications

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be …

Protein Kinase Mzeta (Pkm-Ζ) Regulates Kv1.2 Dependent Cerebellar Eyeblink Classical Conditioning, Kutibh Chihabi

Graduate College Dissertations and Theses

Learning and memory has been a topic that has captured the attention of the scientific and public communities since the dawn of scientific discovery. Without the faculty of memory, mammals cannot experience nor function in the world; among homosapiens specifically, language, relationships, and personal identity cannot be developed (Eysenck, 2012). After all, some philosophers such as John Locke argued we are nothing but a collection of past memories in which we have developed and improved upon (Nimbalkar, 2011).

Understanding the cellular mechanisms behind learning, and the subsequent formation of memory, has been a topic that has garnered scientific interest for …

Pearls And Perils Of Pupillometry Using A Webcam, Mason Kadem, Rhodri Cusack

Undergraduate Honors Posters

Current methods to measure infants’ cognitive repertoire (i.e., collection of cognitive abilities) are limited. Previous testing paradigms required acquisition of non-age contextualized responses, and relied on measures that involved acquisition of other functions (e.g., language, motor). In addition to response limitations, cognitive functions may be difficult to observe in infants due to the difficulty in infant recruitment. Online testing has increased infant recruitment efforts and physiological responses have bypassed the motor, behavioural and linguistic limitations of infants. Recently, it has been shown that heart rate measures can be acquired through a webcam. Another feasible and reliable physiological measure is pupillometery, …

A Behavioral And Neuroimmune System Model Of The Effects Of Chronic Low-Level Lead Exposure In Young Male C57bl/6j Mice, Mayra Gisel Flores-Montoya

Open Access Theses & Dissertations

Chronic low-level lead exposure reduces memory in children however the brain mechanisms mediating these effects are not known. In previous studies we showed that early lead exposure reduced olfactory memory and exploratory behavior in young mice, and reduced microglia cell density in hippocampus/dentate gyrus. The present studies aimed to identify additional behavioral tests that were sensitive to early low-level lead exposure in young mice; and to examine whether microglia upregulated factors known to promote cell migration. Seventy-two C57BL/6J male mice were exposed to 0 ppm (controls), 30 ppm (low-dose), or 430 ppm (high-dose) of lead acetate via dams' milk from …

Learning, Memory, Cognition, And The Question Of Sentience In Fish, Robert Gerlai

Animal Sentience

Evolutionarily conserved features have been demonstrated at many levels of biological organization across a variety of species. Evolutionary conservation may apply to complex behavioral phenomena too. It is thus not inconceivable that a form of sentience does exist even in the lowest order vertebrate taxon, the teleosts. How similar it is to human sentience in its level of complexity or in its multidimensional features is a difficult question, especially from an experimental standpoint, given that even the definition of human sentience is debated. Woodruff attempts a Turing-like test of fish sentience, and lists numerous neuroanatomic, neurophysiological and behavioral similarities between …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …