Neurosciences Commons^™

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …

Using A Novel Optogenetic Approach To Directly Assess 5-Ht1a Somatodendritic Autoreceptor Function In Response To Chronic Selective Serotonin Reuptake Inhibitor Treatment, Kelly Marie Mcgregor

Wayne State University Dissertations

Antidepressant drugs are widely used but their mechanism of action remains only partially understood. One leading hypothesis holds that a key effect of chronic treatment with a Selective Serotonin Reuptake Inhibitor (SSRI) is loss of somatodendritic 5-HT1A receptor-mediated autoinhibition in serotonergic neurons of the dorsal raphe nucleus (DRN). However, technical limitations have prevented direct testing of this hypothesis. In the current study we took advantage of optogenetic strategies to assess the effects of the classic SSRI fluoxetine on 5-HT1A receptor-mediated autoinhibition. We conducted these experiments in mice expressing the light-sensitive ion channel Channelrhodopsin (ChR) in 5-HT neurons to facilitate their …

Neuroscience, Mindreading, And The Courts: The Example Of Pain, Henry T. Greely

Journal of Health Care Law and Policy

No abstract provided.

Targeting Methylglyoxal And Ppar Gamma To Alleviate Neuropathic Pain Associated With Type 2 Diabetes, Ryan B. Griggs

Theses and Dissertations--Physiology

Neuropathic pain affects up to 50% of the 29 million diabetic patients in the United States. Neuropathic pain in diabetes manifests as a disease of the peripheral and central nervous systems. The prevalence of type 2 diabetes is far greater than type 1 (90%), yet the overwhelming focus on type 1 models this has left the mechanisms of pain in type 2 diabetes largely unknown. Therefore I aimed to improve the current mechanistic understanding of pain associated with type 2 diabetes using two preclinical rodent models: Zucker Diabetic Fatty rats and db/db mice. In addition, I highlight the translational importance …

Panel 1: Legal And Neuroscientific Perspectives On Chronic Pain, David Seminowicz, Amanda Pustilnik, Stephen Rigg, Andre Davis, Karen D. Davis, Hank Greely

Journal of Health Care Law and Policy

No abstract provided.

Panel 2: “Excess” Pain, Hyperalgesia, And The Variability Of Subjective Experience, Amanda Pustilnik, David Seminowicz, Stephen Rigg, Joel Greenspan, Morris Hoffman, Adam Kolber, Michael Pardo

Journal of Health Care Law and Policy

No abstract provided.

Panel 3: Chronic Pain, “Psychogenic” Pain, And Emotion, David Seminowicz, Amanda Pustilnik, M. Kaylie Gioioso, Jennifer Chandler, Robert Dinerstein, Jennifer A. Haythornthwaite, Tor D. Wager

Journal of Health Care Law and Policy

No abstract provided.

Panel 4: Translational Expectations And Issues: Making It Work In Practice, Amanda Pustilnik, David Seminowicz, M. Kaylie Gioioso, Martha Farah, Nancy Gertner, Stacey Tovino

Journal of Health Care Law and Policy

No abstract provided.

An Investigation Of The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

Effects Of Aggregated Alpha-Synuclein On Cultured Neuronal Cells, David Freeman

Dissertations

α-synuclein dysregulation is a critical aspect of Parkinson's disease pathology. Recent studies have observed that α-synuclein aggregates are cytotoxic to cells in culture and that this toxicity can be spread between cells. However, the molecular mechanisms governing this cytotoxicity and spread are poorly characterized. Recent studies of viruses and bacteria, which achieve their cytoplasmic entry by rupturing intracellular vesicles, have utilized the redistribution of galectin proteins as a tool to measure vesicle rupture by these organisms. Using this approach, we demonstrate that α-synuclein aggregates can induce the rupture of lysosomes following their endocytosis in neuronal cell lines. This rupture can …

Extended Treatment Window Exists For Improving Sensorimotor Recovery Using Anti-Nogo A Immunotherapy In Adult Rats With Chronic Stroke Deficits, Katherine Marie Podraza

Dissertations

Stroke related death ranks as the fourth most common cause of mortality in the United States. Current therapeutic options following stroke are limited. One potential therapy involves the use of anti-Nogo-A immunotherapy post-stroke. Our laboratory has shown that the administration of this novel treatment results in sensorimotor recovery in adult and aged rats. This therapy has been shown to be efficacious when applied immediately, 24 hours, and 1 week post-stroke in rats with mild to moderate sensorimotor deficits. In addition, recent results suggest that administration of anti-Nogo-A immunotherapy up to 9 weeks after stroke still induces functional recovery and neuroanatomical …

Bracing Of The Trunk And Neck Has A Differential Effect On Head Control During Gait, S. Morrison, D. M. Russell, K. Kelleran, M. L. Walker

Rehabilitation Sciences Faculty Publications

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk …

Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien

Theses and Dissertations

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell …

Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala

Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS …

The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

A New Obesity Model Reveals The Hypophagic Properties Of Pacap Involve The Regulation Of Homeostatic Feeding In The Ventromedial Hypothalamic Nucleus And Hedonic Feeding In The Nucleus Accumbens, Matthew M. Hurley, Brian Maunze, Jon M. Resch, Mogen M. Frenkel, M. J. Reilley, Megan E. Block, David A. Baker, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Binge eating in humans is a complex disorder that often involves discrete, compulsive feeding sessions of highly palatable foods even in the absence of a deprivation state or hunger. Binging can be effectively modeled in rodents by providing subjects with limited access to a palatable food source (Western Diet; WD) as an adjunct to ad lib access to normal chow (Standard Chow; SC). Although this design recapitulates several fundamental characteristics observed in binge eating disorder, the binge eating observed in this paradigm is likely a product of both hedonic and homeostatic drives with the need to balance energy stores still …

Expression Patterns Of Bdnf With Central Anorexigenic Signaling Pathways Involving Pacap In The Hypothalamic Ventromedial Nuclei, Brian Maunze, Matthew M. Hurley, Jon M. Resch, M. J. Reilley, E. M. Wassmann, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid polypeptide belonging to the secretin super family of peptides. PACAP binds to its type 1 receptor (PAC1R) with greater affinity than for the receptors for vasoactive intestinal polypeptides (VIP), VPAC1 and VPAC2. Although mRNA for PACAP and its receptor PAC1R are found throughout the central nervous system, they are abundantly expressed in the hypothalamic ventromedial nuclei (VMN). In male Sprague Dawley rats, infusions of PACAP into the VMN produce a robust decrease in food intake with concomitant increased energy expenditure, decreased body weight, and significantly elevated brain-derived neurotrophic factor (BDNF) mRNA …

Pacap And Cocaine Reinstatement: A Neuropeptide Expressed By Corticostriatal Neurons That Regulates Nucleus Accumbens Astrocytes, Linghai Kong, E. Hess, Brian Maunze, Matthew M. Hurley, Khadijah Makky, Sujean Choi, John R. Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Drug addiction involves heightened relapse vulnerability arising from persistent drug-induced neuro-adaptations, including a) hypofrontality which is thought to reflect reduced firing of cortical afferents to the nucleus accumbens (NAcc) and b) altered glutamate homeostasis in NAcc that likely involves reduced glutamate release and uptake by astrocytes. An important question is whether these forms of pathological plasticity are functionally linked such that reduced corticostriatal firing may result in aberrant regulation of astrocytes in the NAcc. To begin to evaluate this possibility, we first determined whether neurons regulate system xc- (Sxc) activity, a mechanism of non-vesicular glutamate release by astrocytes. We found …

Neural Correlates Of Episodic Memory Formation In Children And Adults, Lingfei Tang

Wayne State University Theses

The medial temporal lobe (MTL) and prefrontal cortex (PFC) are two key brain regions that support episodic memory formation in both children and adults, but the functional developmental of these regions remains unclear. In this study, we investigated the development of neural correlates of episodic memory formation using functional MRI with a subsequent memory paradigm, administered to a cross-sectional sample of 83 children and adults. We found that MTL subregions showed an age-related increase in activation supporting memory formation of complex scenes. In addition, a functionally defined scene-sensitive region in the posterior MTL also showed similar increase and predicted better …

Using The Symmetry Of False Matches To Solve The Correspondence Problem, Cherlyn J. Ng, Bart Farell

Biomedical and Chemical Engineering - All Scholarship

Veridical stereoscopic depth depends on matching corresponding image points. This requires solving the stereo correspondence problem: how are true matches distinguished from false ones? Conventional algorithms select true matches on the basis of feature detection [what do you mean by ‘feature detection’ here? Is there some more specific term?] and adherence to natural statistics. They reject false matches as noise. We propose here an alternative that uses the signals present in false matches to delineate the true solution. When visualized in a Keplerian array, binocular matches are symmetrically reflected about an axis that is a potential solution. Properties such as …