Medicine and Health Sciences Commons^™

Role Of Membrane Gm1 On Early Neuronal Membrane Actions Of Aβ During Onset Of Alzheimer's Disease, E. J. Fernandez-Perez, Fernando Sepulveda, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p < 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p < 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p < 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, …

Corticosterone Regulates Both Naturally Occurring And Cocaine‐Induced Dopamine Signaling By Selectively Decreasing Dopamine Uptake, Daniel S. Wheeler, Amanda L. Ebben, Beliz Kurtoglu, Marissa E. Lovell, Austin T. Bohn, Isabella A. Jasek, David A. Baker, John R. Mantsch, Paul J. Gasser, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine's effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic …

Extending The Family: Roles For Uptake2 Transporters In Regulation Of Monoaminergic Signaling, Paul J. Gasser, Lynette C. Daws

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Editorial For The Special Issue: Monoamine Transporters In Health And Disease, Paul J. Gasser, Lynette C. Daws

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Evaluating Motivational Interviewing In The Physician Assistant Curriculum, Patrick Halbach, Abiola O. Keller

Physician Assistant Studies Faculty Research and Publications

Purpose Motivational interviewing (MI) is an evidence-based technique that enables clinicians to help patients modify health behaviors. Although MI is an essential tool for physician assistants (PAs), the extent to which it is addressed in PA curricula in the United States is unknown. This study is a comprehensive description of MI education in PA programs in the United States.

Methods Data are from the 2014 Physician Assistant Education Association Annual Program Survey. Descriptive statistics were conducted on de-identified data from all 186 PA programs in the United States.

Results Of the 186 PA programs surveyed, 72.58% (n = 135) reported …

Aging, Executive Function, Fronto-Parietal Network Cortical Thickness: Insights From Cognitive Reserve, Katherine Reiter

Dissertations (1934 -)

Cognitive reserve (CR) indexes the nonlinear relationship between neurological insult and behavioral change. CR is manifested in both static factors (e.g., childhood environment, education) and modifiable lifestyle factors, (e.g., leisure activities). Detailed investigation of the influence of CR on cortical thickness, which indexes neuropathology, and cognitive functioning could be particularly important in understanding the heterogeneity of Alzheimer’s disease (AD). While memory decline is the hallmark of AD, executive functioning (EF) decline often predates memory changes, making EF an important target for investigating CR influences. The current study examines the relationship of CR and genetic risk for AD (ε4) on EF …

Markerless Kinematics Of Pediatric Manual Wheelchair Mobility, Jacob Robert Rammer

Dissertations (1934 -)

Pediatric manual wheelchair users face substantial risk of orthopaedic injury to the upper extremities, particularly the shoulders, during transition to wheelchair use and during growth and development. Propulsion strategy can influence mobility efficiency, activity participation, and quality of life. The current forefront of wheelchair biomechanics research includes translating findings from adult to pediatric populations, improving the quality and efficiency of care under constrained clinical funding, and understanding injury mechanisms and risk factors. Typically, clinicians evaluate wheelchair mobility using marker-based motion capture and instrumentation systems that are precise and accurate but also time-consuming, inconvenient, and expensive for repeated assessments. There is …

The Neural Encoding Of Reward In The Striatal-Pallidal Circuitry, Chung Lung Chan

Dissertations (1934 -)

Humans and animals are constantly exposed to external stimuli. The ability to process reward value of a stimulus is critical to guiding appropriate behavior and essential for survival. These processes are regulated by neuronal activity and neurochemical signaling in the reward circuitry, particularly in the nucleus accumbens (NAc). The NAc receives dopaminergic inputs from the midbrain ventral tegmental area (VTA) and sends GABAergic projections to the ventral pallidum (VP). Electrophysiological studies have characterized phasic neuronal responses in the NAc that differential encode appetitive and aversive taste stimuli. Exposure to an appetitive taste stimulus evoked predominantly phasic inhibitory responses in the …

Neuromuscular Function In Women Postpartum, Rita Deering

Dissertations (1934 -)

Efficient abdominal muscle function is important for functional mobility in men and women, and dysfunction of these muscles has been associated with impaired function such as low back pain. This dissertation explored abdominal muscle function in healthy young men and young women who have never been pregnant (nulligravid). As pregnancy and child birth also impact the tissues of the abdominal wall, this dissertation will also explore abdominal muscle function in postpartum women. This dissertation involved three primary aims. Aim1 compared abdominal muscle function and experimental pain perception in males and nulligravid females. Maximal strength over a range of trunk angles, …

Organic Cation Transporter 3 (Oct3) Is Localized To Intracellular And Surface Membranes In Select Glial And Neuronal Cells Within The Basolateral Amygdaloid Complex Of Both Rats And Mice, Paul J. Gasser, Matthew M. Hurley, June Chan, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. …

The Application Of Crispr Technology To High Content Screening In Primary Neurons, Ben L. Callif, Brian Maunze, Nick L. Krueger, Matthew T. Simpson, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon growth is coordinated by multiple interacting proteins that remain incompletely characterized. High content screening (HCS), in which manipulation of candidate genes is combined with rapid image analysis of phenotypic effects, has emerged as a powerful technique to identify key regulators of axon outgrowth. Here we explore the utility of a genome editing approach referred to as CRISPR (Clustered Regularly Interspersed Palindromic Repeats) for knockout screening in primary neurons. In the CRISPR approach a DNA-cleaving Cas enzyme is guided to genomic target sequences by user-created guide RNA (sgRNA), where it initiates a double-stranded break that ultimately results in frameshift mutation …

Regulation Of System Xc-By The Neuropeptide Pacap: Implications For Glutamate Transmission In Drug Addiction, Linghai Kong

Dissertations (1934 -)

Drug addiction is a chronic brain disorder characterized by heightened relapse susceptibility. Drug-induced aberrant glutamate signaling in corticostriatal circuitry contributes to behaviors in virtually every preclinical model of drug seeking and correlates with drug craving in human. Here, we propose that glutamate signaling is a product of integrated activity between neurons and astrocytes, such that disruptions within astrocytes can stem from abnormal neuronal signaling (e.g., altered corticostriatal firing) and be the source of additional disruptions in other neuronal circuits. The astrocytic mechanism studied in these experiments is system xc- (Sxc) since drug-induced changes to this non-vesicular glutamate release mechanism contribute …

Combined Chondroitinase And Klf7 Expression Reduce Net Retraction Of Sensory And Cst Axons From Sites Of Spinal Injury, Zimei Wang, Kristen N. Winsor, Evan Hess, Murray G. Blackmore, Christopher Nienhaus

Biomedical Sciences Faculty Research and Publications

Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors. For example, a transcriptionally active chimera of Krüppel-like Factor 7 (KLF7) and a VP16 domain improves axon growth when expressed in corticospinal tract neurons. Here …

Corticosterone Potentiation Of Cocaine-Induced Reinstatement Of Conditioned Place Preference In Mice Is Mediated By Blockade Of The Organic Cation Transporter 3, Jayme R. Mcreynolds, Analisa Taylor, Oliver Vranjkovic, Terra Ambrosius, Olivia Derricks, Brittany Nino, Beliz Kurtoglu, Robert A. Wheeler, David A. Baker, Paul J. Gasser, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using …

Long Days Enhance Recognition Memory And Increase Insulin-Like Growth Factor 2 In The Hippocampus, Adriano Dellapolla, Ian Kloehn, Harshida Pancholi, Ben L. Callif, David Wertz, Kayla Rohr, Matthew M. Hurley, Kimberly Baker, Samer Hattar, Marieke R. Gilmartin, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered …