Life Sciences Commons^™

Investigating The Roles Of The Dorsal And Ventral Striatum In Humor Comprehension And Appreciation Throughout Health, Aging, And Parkinson’S Disease, Maggie Prenger

Electronic Thesis and Dissertation Repository

Humor processing is thought to involve two distinct components. The first, humor comprehension, involves detecting and resolving incongruities that are present within a humorous stimulus. This is related to cognitive processes such as ambiguity resolution, response inhibition, working memory, and cognitive flexibility, functions that are mediated in part by the dorsal portion of the striatum (DS). Humor appreciation, on the other hand, refers to the subjective amusement and mirth that one experiences in response to a joke. This is related to reward processing, which implicates the ventral portion of the striatum (VS). Across three separate studies, we investigated the involvement …

The Effect Of Postural Perturbations On Cardiovascular And Skeletal Muscle Function In Healthy Adults, Patrick Siedlecki

Electronic Thesis and Dissertation Repository

Maintenance of standing balance is vital to daily living. Traditionally, perspectives on maintaining balance are achieved through the study of visual, vestibular and somatosensory inputs on motor outputs. While evidence suggests cardiovascular regulation also functions to assist postural control during orthostatic stress, how the cardiovascular system responds to postural perturbations is not well established. This dissertation includes four studies that investigated the effects of postural perturbations on the cardiovascular system and skeletal muscle responses in healthy adults. All of the studies involved exposing standing participants to surface-translation perturbations at different velocities, with known or unknown timing, and occurred while spontaneously …

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

Regulation Of Endoplasmic Reticulum Stress In Saccharomyces Cerevisiae, Sarah R. Chadwick

Electronic Thesis and Dissertation Repository

The budding yeast Saccharomyces cerevisiae has been used extensively to uncover the genetic mechanisms that control basic cellular processes, including survival, maintenance, and response to stressors. One metric of yeast survival is chronological lifespan (CLS), which is the amount of time non-dividing yeast cells can survive at stationary phase. Variations in CLS following genetic alteration are used to understand the function of specific genes and pathways in cellular aging. Many factors contribute to aging, including accumulation of toxic misfolded secretory proteins in the endoplasmic reticulum (ER stress), to which the cell responds through activation of ER stress signaling pathways, such …

Investigating The Role Of Pannexin 3 In Intervertebral Disc Health And Disease, Meaghan E. Serjeant

Electronic Thesis and Dissertation Repository

Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in intervertebral discs (IVDs), its function here remained unknown. Using Panx3^-/- mice, this study investigated the role of Panx3 in age-associated and injury-induced models of IVD degeneration. While loss of Panx3 did not significantly impact the progression of age-associated IVD degeneration, it was associated with a protective phenotype in an injury model of IVD degeneration, specifically in the annulus fibrosus (AF). Following IVD injury, WT mice showed an accumulation of enlarged cells that appeared to contribute to disrupted AF …

Assessing Cognitive Function In Chronic Sport-Related Head Impacts And Aging, Danielle Brewer-Deluce

Electronic Thesis and Dissertation Repository

Healthy normal aging and cumulative head trauma (concussion and subconcussion), can influence cognition independently and concomitantly leading to substantial late-life cognitive impairments (e.g., as seen in increased rates of dementia). With this as motivation, this dissertation explores three aspects of aging, head injury and cognition using the Cambridge Brain Sciences (CBS) cognitive battery (www.cambridgebrainsciences.com).

Study 1 (Chapter 2): Concussion-specific testing combines assessments from multiple domains to evaluate a variety of functions. While clinically relevant, their succinct nature limits the amount of cognitive information available. Eighteen male football athletes were examined at baseline using the Sport Concussion Assessment Tool (SCAT) 3, …

The Effect Of Age On Social Behaviour In Drosophila Melanogaster And The Progeny Of Aged Parents, Dova Brenman

Electronic Thesis and Dissertation Repository

Recent studies have linked neuropsychiatric disorders to older parents. These disorders often include changes in social behaviours like the social spacing between neighbouring individuals, which can be modeled in organisms such as Drosophila melanogaster. I investigated the effects of aging on the social space between neighbouring D. melanogaster and how aging impacts the next generation. To achieve this, I used the social space assay and found that individuals become less social with age and that this effect is passed on to the first generation only. Additionally, accelerating the physiological process of aging via increased rearing temperatures or exposure to …

Genes And Gene Networks Related To Age-Associated Learning Impairments, Raihan Uddin

Electronic Thesis and Dissertation Repository

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI …

Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub

Electronic Thesis and Dissertation Repository

The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression …

The Effect Of A Combined Multiple-Modality Exercise Intervention On Sensorimotor Function In Community Dwelling Older Adults, With A Subjective Cognitive Complaint: The M4 Study (Multi-Modal; Mind Motor), Sam Titheridge

Electronic Thesis and Dissertation Repository

Aging is associated with the increased onset of diseases such as cognitive impairment, and ultimately dementia. Participants, 55+ years, with a self-reported cognitive complaint completed a 6-month exercise intervention. They were randomized to either a multiple modality exercise program (M2), consisting of aerobic, stretching and balancing exercises or a multiple modality plus mind motor program (M4), whereby a square stepping exercise was incorporated. Participants were assessed for reaction time (RT), movement time (MT) and % errors at baseline and at 6-months using an eye tracking 1000 system. Participants performed prosaccades and antisaccades (AS). AS RT was significantly quicker from baseline …

The Effects Of A Multiple-Modality Mind-Motor Program On Vascular Outcomes In Community-Dwelling Older Adults With Subjective Cognitive Complaints, Amanda M. Deosaran

Electronic Thesis and Dissertation Repository

Studies have found a link between cardiovascular risk factors (CVRFs) and Alzheimer’s disease however; the mechanism by which CVRFs increase the risk of cognitive decline is not fully understood. The current study attempts to improve CVRFs in order to enhance cognition in older adults. Primary outcomes include ambulatory and clinical resting systolic and diastolic blood pressure (SBP; DBP). In total, 89 community-dwelling older adults with subjective cognitive complaints were randomized to either a multiple-modality mind-motor (M4) exercise or a multiple-modality (M2) exercise only. Significance was found in nighttime peak SBP (6.55 mmHg, p=.04) between groups, with a decrease in M2 …

Decreased Peak Muscle Power Is Associated With Motor Unit Loss In The Lower Limb Of Older Adults, Neal B. Mckinnon

Electronic Thesis and Dissertation Repository

This study investigated the relationship between motor unit (MU) properties and the strength and power of two lower limb muscles in healthy young and old adults. Twelve older adults (mean age, 77 ± 5 yrs) and twelve young adults (mean age, 24 ± 3 yrs) were studied. MU properties of the tibialis anterior (TA) and vastus medialis (VM) muscles were determined using decomposition-enhanced spike-triggered averaging (DE-STA). Motor unit number estimates (MUNE) of the TA were significantly reduced (p>0.05) in older adults (102 ± 76) compared to young adults (234 ± 109), primarily as a result of significantly larger surface-detected …

Quantifying The Effect Of Age And Contraction Mode On The Force-Velocity-Power Relationship In The Knee Extensors, Justin R. Paturel

Electronic Thesis and Dissertation Repository

PURPOSE: To assess and compare the force-velocity-power relationship (F-V-P) using isotonic and isokinetic knee extensions in 11 younger (19-30y) and 11 older (69-81y) men. METHODS: The construction of the F-V-P curves were attained with each participant performing maximal, explosive knee extensions at 8 different loads (isotonic) and 8 different velocities (isokinetic) on a Cybex HUMAC NORM dynamometer. Maximal voluntary contraction (MVC or P_o), maximal shortening velocity (V_max), maximum power, optimal torque (P_opt) and velocity (V_opt) were assessed and compared. RESULTS: The older men were 43% weaker, 18% slower and ~54% less powerful …

The Effects Of Age And Long-Term Endurance Training On Vo2 Kinetics, Tyler M. Grey

Electronic Thesis and Dissertation Repository

The kinetics of the adjustment of pulmonary oxygen uptake (VO₂) was examined during step transitions from 20 W to moderate-intensity cycling in young (Y), middle-aged (M), and older (O) endurance trained and untrained men. VO_2p was measured breath-by-breath and changes in deoxygenated hemoglobin ([HHb]) were measured by near-infrared spectroscopy. VO_2p and [HHb] were modeled with a monoexponential model. The kinetic time constant for VO₂ (τVO_2p) was not different across age-groups (P > 0.05) in the trained group (17 ± 8, 18 ± 5, and 20 ± 5 s, in Y, M, and O, respectively). …

Electromechanical Delay Of The Dorsiflexors In Young And Old Women, In H. Choi

Electronic Thesis and Dissertation Repository

PURPOSE: The aim of the current study was to examine the effect on electromechanical delay (EMD) in the dorsiflexors of young and old women during maximal isometric voluntary and electrically evoked contractions, and after a bout of lengthening contractions. METHODS: Nine young (25.1±1.3 years) and nine old (68.3±6.1 years) women performed baseline isometric contractions with evoked twitches followed by a series of dynamic lengthening contractions using a Biodex multi-joint dynamometer. Maximal isometric voluntary and evoked contractions were measured to assess EMD. Time points were recorded at baseline, mid-point of the intervention, post-task termination, and during recovery at 0.5, 2, 10, …

Aging And Obesity Models In Osteoarthritis, Sara Ohora

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a degenerative joint disease whose exact mechanisms are not well understood, but aging and obesity are common risk factors. To determine the role of transforming growth factor-alpha (TGFα) in obesity-associated OA, Tgfa null and control mice on control and high fat diets were compared. In addition, spontaneous OA was investigated in aging C57BL/6J mice. Quantitative magnetic resonance was used to assess body composition in the obesity model, while gait analysis, histological staining and OARSI scoring were used to determine OA in both models. Mice on high fat diet developed no OA, but Tgfa null mice weighed significantly …

The Chromatin Remodeling Protein Atrx In Development And Maintenance Of Mouse Skeletal Tissues, Lauren A. Solomon

Electronic Thesis and Dissertation Repository

Alpha-thalassemia X-linked mental retardation (ATR-X) syndrome is a rare genetic disorder associated with severe developmental delay, mental retardation and craniofacial dysmorphism. This syndrome is caused by mutations in the ATRX gene which encodes a member of the SWI/SNF family of chromatin remodeling proteins. ATR-X patients exhibit dwarfism and skeletal defects, including hand and foot deformities. I hypothesized that the skeletal deformities in ATR-X syndrome are due to a direct role of ATRX in the development of the skeleton. My objective was to characterise skeletal phenotypes observed in three animal models conditionally deficient for ATRX in different skeletal tissues. Mice lacking …

Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann

Electronic Thesis and Dissertation Repository

The longevity associated protein p66Shc has been suggested to regulate organismal lifespan through initiation of apoptotic pathways. Following stress-induced translocation into the mitochondria, p66Shc promotes increased reactive oxygen species (ROS) production and triggers poorly defined downstream signaling events that lead to decreased cell viability. Protein disulfide bonding has recently emerged as aROSdependent post-translational modification that regulates protein function and signaling processes. Using the mouse hippocampal HT-22 cell line, I sought to determine the changes in the disulfide proteome associated with p66Shc mediatedROSproduction. Through Redox 2D-SDSPAGEanalysis of mitochondrial and cytosolic extracts, redox sensitive proteins altered by p66Shc mediatedROSformation were identified. Of …

Neuromuscular Function Following Lengthening Contractions, Geoffrey A. Power

Electronic Thesis and Dissertation Repository

Unaccustomed lengthening contractions have been shown to impair muscle function - however little is known regarding this impairment on muscle power - specifically, the velocity component of power during voluntary contractions in humans. The four studies presented in my thesis investigated power-loss following lengthening contractions in healthy young and old women and young men.

The purpose of Study 1 was to determine reliability of velocity-dependent power of the dorsiflexors using the isotonic mode of the Biodex Dynamometer. I determined the isotonic mode is reliable and can be used to track changes in velocity and power following fatigue and lengthening contractions. …

Neuroprotective Effects Of Long-Term Endurance Training On The Cortical Autonomic Network In The Aging Brain, Torri A. Luchyshyn

Electronic Thesis and Dissertation Repository

This study tested whether long-term endurance training in older adults (ET; n = 15, 55 ± 4 years, relative VO₂max = 50 ± 8 ml/kg/min) would alter cardiovagal control and preserve the cortical autonomic network compared to age-matched controls (CON; n = 15, 56 ± 4 years, relative VO₂max = 37 ± 9 ml/kg/min). The hypothesis predicts 1) altered deactivation patterns of the ventral medial prefrontal cortex (vMPFC) in response to isometric hand grip (IHG) and 2) greater indices of cardiovagal control; a) increased baroreflex sensitivity at rest, b) greater heart rate change (ΔHR) and c) …