Neurosciences Commons^™

Acute Inhibition Of Estradiol Synthesis Impacts Vestibulo-Ocular Reflex Adaptation And Cerebellar Long-Term Potentiation In Male Rats, Cristina V. Dieni, Aldo Ferraresi, Jacqueline A. Sullivan, Sivarosa Grassi, Vito E. Pettorossi, Roberto Panichi

Brain and Mind Institute Researchers' Publications

© 2017, The Author(s). The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF …

The Role Of The Leukemia Inhibitory Factor Receptor In Neuroprotective Signaling, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison. This review examines the role of this receptor in the CNS and immune system, and its …

Treatment Of Glenohumeral Arthritis Pain Utilizing Spinal Cord Stimulation., Stephen T Susa, Chris S Karas, Nathaniel K Long

Neuroscience Articles

BACKGROUND: Dorsal column stimulation may be utilized to treat non-neuropathic pain attributed to glenohumeral arthritis.

CASE DESCRIPTION: An 84-year-old female presented with right shoulder pain for 3 years. She was diagnosed with glenohumeral arthritis and a complete loss of the joint space. She was treated with a dorsal column stimulator, requiring the electrodes to be placed from the inferior aspect of C3 to the superior aspect of T1. Six weeks postoperatively, she reported >90% coverage of her shoulder pain, demonstrated increased right arm function, and a reduction in her use of narcotics.

CONCLUSION: Dorsal column stimulation of C3-T1 proved to …

Comparison Of Disease-Modifying Therapies For The Management Of Multiple Sclerosis: Analysis Of Healthcare Resource Utilization And Relapse Rates From Us Insurance Claims Data., Jacqueline Nicholas, Aaron Boster, Ning Wu, Wei-Shi Yeh, Monica Fay, Jon Kendter, Ming-Yi Huang, Andrew Lee

Neuroscience Articles

BACKGROUND: Data on comparative healthcare resource utilization and costs associated with the newer oral disease-modifying therapies (DMTs) for managing relapsing-remitting multiple sclerosis (MS) in routine clinical practice are limited. The purpose of this study was to estimate healthcare resource utilization, costs, and relapse rates in the year after initiating treatment with dimethyl fumarate (DMF), interferon (IFN)-β, glatiramer acetate (GA), teriflunomide, or fingolimod in routine clinical practice for patients with MS who did not receive a DMT in the previous year.

METHODS: Patients initiating DMF, IFNβ, GA, teriflunomide, or fingolimod were identified based on claims data from 2012 to 2015 in …

Vmpfc Activation During A Stressor Predicts Positive Emotions During Stress Recovery, Xi Yang, Katelyn M. Garcia, Youngkyoo Jung, Christopher T. Whitlow, Kateri Mcrae, Christian E. Waugh

Psychology: Faculty Scholarship

Despite accruing evidence showing that positive emotions facilitate stress recovery, the neural basis for this effect remains unclear. To identify the underlying mechanism, we compared stress recovery for people reflecting on a stressor while in a positive emotional context with that for people in a neutral context. While blood–oxygen-level dependent data were being collected, participants (N = 43) performed a stressful anagram task, which was followed by a recovery period during which they reflected on the stressor while watching a positive or neutral video. Participants also reported positive and negative emotions throughout the task as well as retrospective thoughts …

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion …

Repeat-Associated Non-Aug (Ran) Translation And Other Molecular Mechanisms In Fragile X Tremor Ataxia Syndrome, M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA …

Putative Adult Neurogenesis In Old World Parrots: The Congo African Grey Parrot (Psittacus Erithacus) And Timneh Grey Parrot (Psittacus Timneh), Pedzisai Mazengenya, Adhil Bhagwandin, Paul R. Manger, Amadi O. Ihunwo

Brain and Mind Institute

In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus) and Timneh grey parrot (Psittacus timneh) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in …

Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler

Department of Neuroscience Faculty Papers

Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic …

Predicting Risk Factors Of Working Aged Hemorrhagic Stroke Patients In A Tertiary Teaching Hospital In Chiang Mai, Suphannee Triamvisit, Wilaiwan Chongruksut, Wanarak Watcharasaksilp, Rujee Rattanasathien

Asian/Pacific Island Nursing Journal

Stroke is the third leading cause of morbidity and mortality in Thailand accounting for a significant and increasing share of hospital costs. The purpose of this project is to study the epidemiology of the prevalence and its predicting factors of working aged hemorrhagic stroke (HS) patients admitted at a tertiary teaching hospital in Chiang Mai, Thailand.

We conducted a five-year retrospective descriptive study. The subjects in this study were patients diagnosed with HS, between 15-59 years of age, and admitted to a tertiary teaching hospital in Chiang Mai, Thailand from January 2009 to December 2013. A total of …

Genome-Wide Profiling Reveals Functional Diversification Of ∆Fosb Gene Targets In The Hippocampus Of An Alzheimer's Disease Mouse Model., Jason C. You, Gabriel S. Stephens, Chia-Hsuan Fu, Xiaohong Zhang, Yin Liu, Jeannie Chin

Department of Neuroscience Faculty Papers

The activity-induced transcription factor ∆FosB has been implicated in Alzheimer's disease (AD) as a critical regulator of hippocampal function and cognition downstream of seizures and network hyperexcitability. With its long half-life (> 1 week), ∆FosB is well-poised to modulate hippocampal gene expression over extended periods of time, enabling effects to persist even during seizure-free periods. However, the transcriptional mechanisms by which ∆FosB regulates hippocampal function are poorly understood due to lack of identified hippocampal gene targets. To identify putative ∆FosB gene targets, we employed high-throughput sequencing of genomic DNA bound to ∆FosB after chromatin immunoprecipitation (ChIP-sequencing). We compared ChIP-sequencing results …

Trpm7 Current Inactivation: Evidence For Inside-Out Signaling, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 channels conduct metal cations such as Na+, K+, Ca2+ and Mg2+. In the presence of external Ca2+/Mg2+ TRPM7 has a steeply outwardly rectifying current-voltage (I-V) relation. In the absence of Ca2+/Mg2+ the IV becomes semi-linear. This has been explained by the removal of pore blockade by divalent cations (e.g. Ca2+o/Mg2+o). TRPM7 channels are inhibited by cytoplasmic Mg2+ in a voltage-independent manner, primarily by a reversible reduction in the overall number of conducting channels. Here, we have examined the consequences of external Ca2+ removal and reintroduction on TRPM7 current kinetics. In whole-cell patch clamp with low internal Mg2+, we rapidly …

Inactivation Of Trpm7 Kinase In Mice Results In Enlarged Spleens, Reduced T-Cell Proliferation And Diminished Store-Operated Calcium Entry, Pavani Beesetty, Krystyna Blanka Wieczerzak, Jennifer Gibson, Taku Kaitsuka, Charles Tuan Luu, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca2+ in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell …

Klf6 And Stat3 Co-Occupy Regulatory Dna And Functionally Synergize To Promote Axon Growth In Cns Neurons, Zimei Wang, Vatsal Mehra, Matthew T. Simpson, Brian Maunze, Dan C. Eastwood, Lyndsey Holan, Murray G. Blackmore, Ishwariya Venkatesh

Biomedical Sciences Faculty Research and Publications

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction …

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …

The Challenged Brain Bps 205g, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Early Procedural Pain Is Associated With Regionally-Specific Alterations In Thalamic Development In Preterm Neonates., Emma G Duerden, Ruth E Grunau, Ting Guo, Justin Foong, Alexander Pearson, Stephanie Au-Young, Raphael Lavoie, M Mallar Chakravarty, Vann Chau, Anne Synnes, Steven P Miller

Brain and Mind Institute Researchers' Publications

Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median …

Specific Relationship Between The Shape Of The Readiness Potential, Subjective Decision Time, And Waiting Time Predicted By An Accumulator Model With Temporally Autocorrelated Input Noise, Aaron Schurger

Psychology Faculty Articles and Research

Self-initiated movements are reliably preceded by a gradual buildup of neuronal activity known as the readiness potential (RP). Recent evidence suggests that the RP may reflect subthreshold stochastic fluctuations in neural activity that can be modeled as a process of accumulation to bound. One element of accumulator models that has been largely overlooked in the literature is the stochastic term, which is traditionally modeled as Gaussian white noise. While there may be practical reasons for this choice, we have long known that noise in neural systems is not white – it is long-term correlated with spectral density of the form …

Transspinal Direct Current Stimulation Produces Persistent Plasticity In Human Motor Pathways, Lynda M. Murray, Behdad Tahayori, Maria Knikou

Publications and Research

The spinal cord is an integration center for descending, ascending, and segmental neural signals. Noninvasive transspinal stimulation may thus constitute an effective method for concomitant modulation of local and distal neural circuits. In this study, we established changes in cortical excitability and input/output function of corticospinal and spinal neural circuits before, at 0–15 and at 30–45 minutes after cathodal, anodal, and sham transspinal direct current stimulation (tsDCS) to the thoracic region in healthy individuals. We found that intracortical inhibition was different among stimulation polarities, however remained unchanged over time. Intracortical facilitation increased after cathodal and anodal tsDCS delivered with subjects …