Medicine and Health Sciences Commons^™

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.

Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.

Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

The Challenges Of Nutrition And Aging, Linda C. Tapsell

L. C. Tapsell

From the time of birth and throughout the lifecycle, the human organism depends on food and nutrients to sustain its growth, development and functionality. With increasing knowledge of biological processes within the human body, the term ‘you are what you eat’, takes on more and more meaning. One of the new levels of understanding relates to the interaction of food components with genes to set off cascades of events that affect health and disease (1). This new understanding provides a detailed view of the dynamic relationship between genes and the environment, represented through food. Our health, our lifespan, can be …

Influence Of A Short-Term, Multicomponent Intervention On Balance And Strength Among The Elderly, Pamela C. Webert

Master's Theses and Doctoral Dissertations

Background: Few studies have combined strength and balance training to assess improvement of activities of daily living among subjects over the age of 65. The purpose of this study was to demonstrate how an eight-week balance and strength training program can lead to improvements in activities of daily living among elderly individuals.

Methods: The subjects consisted of 14 elderly women and 3 elderly men who were all residents of an independent living community. There were 10 subjects in the intervention group and 7 subjects in the control group. The intervention group participated in a supervised balance and strength …

Effects Of Thymus Size And Involution On The Contribution Of Recent Thymic Emigrants To The Peripheral T Cell Pool, Michelle L. Bolner

Dissertations & Theses (Open Access)

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens.

The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity.

Mice that express a …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Aging, Neuromuscular Decline, And The Change In Physiological And Behavioral Complexity Of Upper-Limb Movement Dynamics, S. Morrison, K. M. Newell

Rehabilitation Sciences Faculty Publications

Aging is characterized by a general decline in physiological and behavioral function that has been widely interpreted within the context of the loss of complexity hypothesis. In this paper, we examine the relation between aging, neuromuscular function and physiological-behavioral complexity in the arm-hand effector system, specifically with reference to physiological tremor and isometric force production. Experimental findings reveal that the adaptive behavioral consequences of the aging-related functional decline in neurophysiological processes are less pronounced in simple motor tasks which provides support for the proposition that the motor output is influenced by both extrinsic (e.g., task related) and intrinsic (e.g., coordination, …