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The Role Of The Rna-Binding Protein Rho Guanine Nucleotide Exchange Factor In The Cellular Stress Response, Kevin WH Cheung 2014 Western University

The Role Of The Rna-Binding Protein Rho Guanine Nucleotide Exchange Factor In The Cellular Stress Response, Kevin Wh Cheung

University of Western Ontario - Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which the pathological mechanism is heterogeneous and a cure has been elusive. Recent developments have linked specific proteins found in pathological neuronal cytoplasmic inclusions (NCIs) of ALS motor neurons to familial variants of the disease. These proteins, including TAR DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS), and Rho guanine nucleotide exchange factor (RGNEF) share the common characteristic of being RNA-binding proteins that colocalize within NCIs. RGNEF is unique however in also possessing RhoA activation capacity, suggesting a role in the cell stress response. My ...


Advances In Image Acquisition And Filtering For Mri Neuroimaging At 7 Tesla, Andrew T. Curtis 2014 Western University

Advances In Image Acquisition And Filtering For Mri Neuroimaging At 7 Tesla, Andrew T. Curtis

University of Western Ontario - Electronic Thesis and Dissertation Repository

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths.

First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion of ...


Multi-Oscillator Structure Of The Circadian Pacemaker, Carolina Aguila 2014 Northeastern University

Multi-Oscillator Structure Of The Circadian Pacemaker, Carolina Aguila

Biology Master's Theses

Circadian rhythms are an important part of the body's physiological processes. Although circadian rhythms are endogenously generated, they are normally entrained by environmental cycles, most commonly the light/dark (LD) cycle. One important issue is how they are regulated and synchronized within the suprachiasmatic nucleus (SCN), the controlling center in the mammalian brain. Previous studies have shown that mice deficient in an SCN peptide (VIP-/- mice) under constant darkness display disrupted circadian rhythms with a varying phenotype. The extent to which this deficiency affects mice when entrained to LD cycles is less clear. Some effects of the deficiency suggest ...


Mindfulness Meditation Versus Eeg-Alpha Neurofeedback: The Role Of Eeg-Alpha Enhancement In Attentional Control, Theodore Chow 2014 Western University

Mindfulness Meditation Versus Eeg-Alpha Neurofeedback: The Role Of Eeg-Alpha Enhancement In Attentional Control, Theodore Chow

University of Western Ontario - Electronic Thesis and Dissertation Repository

This thesis directly compared two active interventions known to enhance the EEG-Alpha rhythm, mindfulness meditation (MM) with EEG-Alpha enhancement neurofeedback (NFB), relative to a non-active Sham-NFB control. Seventy-three university students were randomized to one of the three 15-minute single-session interventions. Participants were subsequently compared on their ability to enhance EEG-Alpha amplitude as well as regarding Stroop behavioural performance, EEG event-related potentials, and EEG-Alpha event-related desynchronization (ERD) as markers of attentional control. Participants randomized to MM, NFB, and Sham did not differ in their ability to modulate the EEG-Alpha rhythm post-intervention. However, enhancements in EEG-Alpha amplitude were seen within the MM ...


Drk/Dos/Sos Converge With Crk/Mbc/Dced-12 To Activate Rac1 During Glial Engulfment Of Axonal Debris, Tsai-yi Lu, Johnna E. Doherty, Marc R. Freeman 2014 University of Massachusetts Medical School

Drk/Dos/Sos Converge With Crk/Mbc/Dced-12 To Activate Rac1 During Glial Engulfment Of Axonal Debris, Tsai-Yi Lu, Johnna E. Doherty, Marc R. Freeman

GSBS Student Publications

Nervous system injury or disease leads to activation of glia, which govern postinjury responses in the nervous system. Axonal injury in Drosophila results in transcriptional up-regulation of the glial engulfment receptor Draper; there is extension of glial membranes to the injury site (termed activation), and then axonal debris is internalized and degraded. Loss of the small GTPase Rac1 from glia completely suppresses glial responses to injury, but upstream activators remain poorly defined. Loss of the Rac guanine nucleotide exchange factor (GEF) Crk/myoblast city (Mbc)/dCed-12has no effect on glial activation, but blocks internalization and degradation of debris. Here we ...


Mechanisms Of Astrocyte Contribution To Bortezomib-Induced Peripheral Neuropathy, Caleb R. Robinson 2014 Texas Medical Center Library

Mechanisms Of Astrocyte Contribution To Bortezomib-Induced Peripheral Neuropathy, Caleb R. Robinson

UT GSBS Dissertations and Theses (Open Access)

Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma and other non-solid malignancies, alone or in combination with other chemotherapy drugs. Like other chemotherapeutic agents, bortezomib treatment is frequently accompanied by chemotherapy-induced peripheral neuropathy (CIPN) that may be dose-limiting, adversely affecting quality of life and prognosis. The mechanisms behind bortezomib-induced peripheral neuropathy (BIPN) and CIPN overall are largely unknown. Recent findings in other pain models have indicated substantial involvement of glial cells in chronic pain. Although injury models have shown activation of both astrocytes and microglia following insult, research in other CIPN models has shown astrocytic activation ...


Antidepressant Effects Of The Nts1 Agonist Pd149163 In The Forced Swim Test, Lawrence Carey IV 2014 Northern Michigan University

Antidepressant Effects Of The Nts1 Agonist Pd149163 In The Forced Swim Test, Lawrence Carey Iv

NMU Master's Theses

Neurotensin is a neuropeptide that influences monoaminergic neurotransmission in areas of the brain involved in the pathophysiology of depression. The forced swim test is a commonly used screening model for putative antidepressant medications. Drugs that have antidepressant effects in humans reliably decrease the time animals spend in an immobile posture in the forced swim test without increasing general locomotor activity as measured in an open field test. The present study sought to examine the effects of the neurotensin NTS1 receptor agonist PD149163 and the tricyclic antidepressant drug imipramine on immobility in the forced swim test and on locomotor activity ...


Investigating The Primate Prefrontal Cortex Correlates Of Cognitive Deficits In The Ketamine Model Of Schizophrenia, Kevin J. Skoblenick 2014 Western University

Investigating The Primate Prefrontal Cortex Correlates Of Cognitive Deficits In The Ketamine Model Of Schizophrenia, Kevin J. Skoblenick

University of Western Ontario - Electronic Thesis and Dissertation Repository

The World Health Organization has classified schizophrenia as one of the five leading causes of disability worldwide. Afflicting almost 1% of the world’s population, the disease’s greatest impact stems from its reduction in patients’ cognitive faculties. In order to better study these impairments, a pharmacological model has been developed using the NMDA antagonist, ketamine. This disease model successfully recreates the cognitive dysfunction of schizophrenia, allowing researchers to search for associated electrophysiological changes.

In this project I examined the behavioural and neurophysiological effects of ketamine on non-human primates performing the anti-saccade task. Success in this task requires a degree ...


Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins 2014 University of Kentucky

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 ...


Effects Of Dfo-Induced Hypoxia On Key Signaling Mediators, Jennifer Candelora 2014 Seton Hall University

Effects Of Dfo-Induced Hypoxia On Key Signaling Mediators, Jennifer Candelora

Seton Hall University Dissertations and Theses (ETDs)

While diseases such as cancer and diabetes, or surgery and traumatic injury can cause hypoxia through a decrease in blood circulation to bodily regions or decrease cardiac output they can also associate with hypoxia-induced pain. Clinically, opioids, such as morphine, are used to modulate pain. The mu-opioid receptors (MORs) are one of three main types of opioid receptors and are key mediators in morphine-induced analgesia. Therefore, in this study, the effect of hypoxia on MOR gene expression was examined using human neuronal cells treated with DFO to create a hypoxic-mimic condition. We found that MOR expression was shown to decrease ...


Proliferation, Migration, And Survival Of Cells In The Telencephalon Of The Ball Python, Python Regius, Thomas B. Bales 2014 California Polytechnic State University

Proliferation, Migration, And Survival Of Cells In The Telencephalon Of The Ball Python, Python Regius, Thomas B. Bales

Master's Theses and Project Reports

Reptiles exhibit neurogenesis throughout the brain during adulthood. However, very few studies have quantified telencephalon-wide neurogenesis in adulthood, and no studies have performed these investigations in snakes. Quantifying neurogenesis in the adult snake is essential to understanding class-wide adult neurogenesis and providing insight into the evolution of this trait. The thymidine analog 5-bromo-2’-deoxyuridine (BrdU) was used to quantify cell proliferation, migration, and survival in the ball python (Python regius). First, to determine the proper dose of BrdU for injection we subcutaneously injected 50mg/kg, 100mg/kg, and 250mg/kg into 15 adult male P. regius. We found the 250mg ...


Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford 2014 University of Tennessee, Knoxville

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at the University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the ...


Less-Structured Time In Children's Daily Lives Predicts Self-Directed Executive Functioning, Jane E. Barker, Andrei D. Semenov, Laura Michaelson, Lindsay S. Provan, Hannah R. Snyder, Yuko Munakata 2014 University of Colorado, Boulder

Less-Structured Time In Children's Daily Lives Predicts Self-Directed Executive Functioning, Jane E. Barker, Andrei D. Semenov, Laura Michaelson, Lindsay S. Provan, Hannah R. Snyder, Yuko Munakata

University Libraries Open Access Fund Supported Publications

Executive functions (EFs) in childhood predict important life outcomes. Thus, there is great interest in attempts to improve EFs early in life. Many interventions are led by trained adults, including structured training activities in the lab, and less-structured activities implemented in schools. Such programs have yielded gains in children's externally-driven executive functioning, where they are instructed on what goal-directed actions to carry out and when. However, it is less clear how children's experiences relate to their development of self-directed executive functioning, where they must determine on their own what goal-directed actions to carry out and when. We hypothesized ...


A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera 2014 Western University

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

University of Western Ontario - Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in ...


Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh 2014 Western University

Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh

University of Western Ontario - Electronic Thesis and Dissertation Repository

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response ...


Roles Of Dopamine D1 And D2, Opioid And Glutamate Nmda Receptor Signaling In The Acquisition And Expression Of Fat- And Glucose-Conditioned Flavor Preferences In Rats And C-Fos Analysis Of The Dopamine Mesotelencephalic And Nigrostriatal Pathways Following Intake Of Sugars And Fats In Rats., Julie Dela Cruz 2014 The Graduate Center, CUNY

Roles Of Dopamine D1 And D2, Opioid And Glutamate Nmda Receptor Signaling In The Acquisition And Expression Of Fat- And Glucose-Conditioned Flavor Preferences In Rats And C-Fos Analysis Of The Dopamine Mesotelencephalic And Nigrostriatal Pathways Following Intake Of Sugars And Fats In Rats., Julie Dela Cruz

Dissertations and Theses, 2014-Present

Systemic administration of the non-competitive NMDA antagonist, MK-801, demonstrated that acquisition, but not expression, were found to affect the orosensory-mediated (flavor/flavor: f/f) fructose-conditioned flavor preference (CFP). The present studies demonstrated a similar outcome when f/f and f/n processes were combined. Fat-CFP and glucose-CFP studies indicated that systemic injections of the NMDA antagonist, MK-801, were able to significantly reduce acquisition, but not expression, of Corn-Oil (CO)-CFP and glucose-CFP. Both studies appear to have mitigated effects on acquisition as compared to the separate orosensory and postingestive CFP studies.

Previous studies found that systemic administration of dopamine (DA ...


Testosterone Treatment Does Not Facilitate Prefrontal Cortex Mediated Cognition In Male Marmosets (Callithrix Jacchus), Matthew LaClair, Jeemin Chang, Agnes Lacreuse 2014 University of Massachusetts Medical School

Testosterone Treatment Does Not Facilitate Prefrontal Cortex Mediated Cognition In Male Marmosets (Callithrix Jacchus), Matthew Laclair, Jeemin Chang, Agnes Lacreuse

UMass Center for Clinical and Translational Science Research Retreat

Aging in men is associated with decreases in serum testosterone (T) and a decline in cognitive abilities. We sought to clarify the relationship between T, aging and cognition using the common marmoset (callithrix jacchus), which has been shown to be a useful model of human aging. Ten castrated male marmosets (ages 3-8) were given weekly injections of either T cypionate dissolved in cottonseed oil (T, n = 5) or cottonseed oil alone (controls, n = 5). Cognitive function was assessed with two tasks, the object reversals (OR) and the delayed response (DR). Marmoset behavior was recorded twice daily using a modified frequency ...


Emotion Regulation Through Meditation, Judson Brewer 2014 University of Massachusetts Medical School

Emotion Regulation Through Meditation, Judson Brewer

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "Can Simply Paying Attention Change Behavior? Emotion and Behavior Regulation through Meditation," Dr. Brewer briefly presents studies that used conventional and real-time fMRI to investigate the neurobiological mechanisms of mindfulness comparing novice and experienced meditators.


Keynote Speaker Presentations: 5th Annual Umass Center For Clinical And Translational Research Retreat (Video), Robert H. Brown Jr., Thomas Grisso 2014 University of Massachusetts Medical School

Keynote Speaker Presentations: 5th Annual Umass Center For Clinical And Translational Research Retreat (Video), Robert H. Brown Jr., Thomas Grisso

UMass Center for Clinical and Translational Science Research Retreat

This video features the full keynote presentations from the 5th Annual UMass Center for Clinical and Translational Science Research Retreat at the University of Massachusetts Medical School (UMMS) in Worcester, MA, on May 20, 2014.

Beginning at 12:40

1st Keynote Speaker: Robert H. Brown, Jr., MD, D.Phil, Chair, Department of Neurology, UMMS. “Lou Gehrig Disease: From Mapping to Medicines”

Beginning at 1:22:19

2nd Keynote Speaker: Thomas Grisso, PhD, Director, Law and Psychiatry Program and Professor, Department of Psychiatry, UMMS. Recipient, Chancellor’s Medal for Distinguished Scholarship. “Translational Research in Law and Psychiatry”

Also included is a ...


Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo 2014 University of Connecticut

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

University Scholar Projects

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model ...


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