Neurosciences Commons^™

Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects Of Cocaine, Aric Madayag, Doug Lobner, Kristen S. Kau, John R. Mantsch, Omer Abdulhameed, Matthew Hearing, Mark D. Grier, David A. Baker

Biomedical Sciences Faculty Research and Publications

Cocaine produces a persistent reduction in cystine–glutamate exchange via system x_c− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System x_c− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system x_c− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine …

Role Of Medial Prefrontal Cortical Group Ii Metabotropic Glutamate Receptor In The Development Of Cocaine Sensitization, Xiaohu Xie

Theses and Dissertations (ETD)

The current studies examined the role of medial prefrontal cortical (mPFC) group II metabotropic glutamate receptors (mGluR_2/3) in the development of cocaine sensitization. Initial studies demonstrated that intra-mPFC injection of the mGluR_2/3 receptor agonist, APDC, dose-dependently reduced acute behavioral response to cocaine (0.015-15 nmol/side with significant effects starting at 1.5nmol/side). The effects of APDC were prevented by intra-mPFC co-injections of an mGluR_2/3 antagonist, LY341495 (1.5 nmol/side). Repeated intra-mPFC APDC (1.5 nmol/side) injections also prevented the initiation of behavioral and neurochemical sensitization, which is defined as enhanced nucleus accumbens (NAc) dopamine response to cocaine. Once sensitization was …

Neuroadaptive Changes In The Mesocortical Glutamatergic System During Nicotine Self-Administration And After Extinction In Rats, Fan Wang

Theses and Dissertations (ETD)

The mesocorticolimbic pathway is critical in almost all aspects of drug abuse, including nicotine. Though many of the neurochemical and molecular effects of nicotine have been well studied, nicotine’s long-term neuroadaptive effects, specifically within the mesocorticolimbic pathway, are largely undefined. Thus, in current study, we determined the neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, and after extinction. In the initial study, after 18 days of nicotine SA, in the medial prefrontal cortex (mPFC), NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% and 83%, …

Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou

Neuroscience, Cell Biology & Physiology Faculty Publications

AIM: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans, and it is highly invasive. Doxycycline, first identified as an antimicrobial agent, is a nonspecific inhibitor of matrix metalloproteinases (MMPs). Our objective was to investigate the anti-MMP effect of doxycycline at therapeutically acceptable levels on glioma cells in vitro.

METHODS: The MTT assay was used to determine the anti-proliferative effects of doxycycline. MMP2 activity and expression were determined by gelatinase zymography and real-time quantitative RT-PCR, respectively. Cell invasion was assessed by Matrigel invasion assay.

RESULTS: Doxycycline exerted mild anti-proliferative effects on all three glioma cell lines …

Perinatal Ph And Neuropsychological Outcomes At Age 3 Years In Children Born Preterm: An Exploratory Study, Kimberly A. Espy, Theresa E. Senn, David A. Charak, Jill Tyler, Sandra A. Wiebe

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The impact of extreme prematurity and related hypoxic-ischemic events on brain development recently has begun to be characterized with modern neuroimaging methods, although comparatively less is known about the neuropathology in those born at heavier birth weights. Even subclinical levels of perinatal hypoxia-ischemia, as indexed by perinatal blood pH, are related to intelligence in school-aged children born preterm. Given the impact of hypoxia-ischemia on white matter and the emerging evidence of specific executive and mathematic deficits in children born preterm, the impact of perinatal hypoxia-ischemia on these outcomes was explored in children at relatively low-risk for sequelae. In a sample …

A Bayesian Multilevel Modeling Approach For Data Query In Wireless Sensor Networks, H. Wang, H. Fang, K. A. Espy, D. Peng, H. Sharif

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

In power-limited Wireless Sensor Network (WSN), it is important to reduce the communication load in order to achieve energy savings. This paper applies a novel statistic method to estimate the parameters based on the realtime data measured by local sensors. Instead of transmitting large real-time data, we proposed to transmit the small amount of dynamic parameters by exploiting both temporal and spatial correlation within and between sensor clusters. The temporal correlation is built on the level-1 Bayesian model at each sensor to predict local readings. Each local sensor transmits their local parameters learned from historical measurement data to their cluster …

Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, S. A. Wiebe, K. A. Espy, D. Charak

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Although many tasks have been developed recently to study executive control in the preschool years, the constructs that underlie performance on these tasks are poorly understood. In particular, it is unclear whether executive control is comprised of multiple, separable cognitive abilities (e.g., inhibition and working memory) or whether it is unitary in nature. A sample of 243 normally developing children between 2.25 and 6 years of age completed a battery of age appropriate executive control tasks. Confirmatory factor analysis (CFA) was used to compare multiple models of executive control empirically. A single-factor, general model was sufficient to account for the …

Augmented Hypothalamic Corticotrophin-Releasing Hormone Mrna And Corticosterone Responses To Stress In Adult Rats Exposed To Perinatal Hypoxia, Hershel Raff, Lauren Jacobson, William E. Cullinan

Biomedical Sciences Faculty Research and Publications

Stressful events before or just after parturition alter the subsequent phenotypical response to stress in a general process termed programming. Hypoxia during the period before and during parturition, and in the postnatal period, is one of the most common causes of perinatal distress, morbidity, and mortality. We have found that perinatal hypoxia (prenatal day 19 to postnatal day 14) augmented the corticosterone response to stress and increased basal corticotrophin-releasing hormone (CRH) mRNA levels in the parvocellular portion of the paraventricular nucleus (PVN) in 6-month-old rats. There was no effect on the levels of hypothalamic parvocellular PVN vasopressin mRNA, anterior pituitary …

Human Parietal "Reach Region" Primarily Encodes Intrinsic Visual Direction, Not Extrinsic Movement Direction, In A Visual Motor Dissociation Task., Juan Fernandez-Ruiz, Herbert C Goltz, Joseph F X Desouza, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to …

Human Mst But Not Mt Responds To Tactile Stimulation, Michael S. Beauchamp, Nafi E. Yasar, Neel Kishan, Tony Ro

Publications and Research

Previous reports of tactile responses in human visual area MT/V5 have used complex stimuli, such as a brush stroking the arm. These complex moving stimuli are likely to induce imagery of visual motion, which is known to be a powerful activator of MT. The area described as “MT” in previous reports consists of at least two distinct cortical areas, MT and MST. Using functional magnetic resonance imaging, we separately localized human MT and MST and measured their response to vibrotactile stimuli unlikely to induce imagery of visual motion. Strong vibrotactile responses were observed in MST but not in MT. Vibrotactile …

Mutations At F637 In The Nmda Receptor Nr2a Subunit M3 Domain Influence Agonist Potency, Ion Channel Gating And Alcohol Action, H. Ren, Ak Salous, J. M. Paul, Rh Lipsky, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

Background and purpose:

NMDA receptors are important molecular targets of ethanol action in the CNS. Previous studies have identified a site in membrane-associated domain 3 (M3) of the NR1 subunit and two sites in M4 of the NR2A subunit that influence alcohol action; the sites in NR2A M4 also regulate ion channel gating. The purpose of this study was to determine whether mutations at the site in the NR2A subunit corresponding to the NR1 M3 site influence alcohol action and ion channel gating.

Experimental approach:

We investigated the effects of mutations at phenylalanine (F) 637 of the NR2A subunit using …

Energizing Mirna Research: A Review Of The Role Of Mirnas In Lipid Metabolism, With A Prediction That Mir-103/107 Regulates Human Metabolic Pathways, Bernard R. Wilfred, Wang-Xia Wang, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon …

Diarrea Viral Bovina Y Animales Portadores Del Virus En Hatos Productores De Leche De La Irrigación De Majes, Arequipa, John C. Huaman G., Hermelinda G. Rivera, Mariluz Araínga, Cesar Gavidia Ch., Alberto Manchego S.

Journal Articles: Pharmacology & Experimental Neuroscience

The objective of this study was to determine the prevalence of bovine viral diarrhea virus (BVDV) and persistently infected (PI) animals in dairy herds located in Majes, Arequipa, Peru. In the first phase, 204 bulk tank milk samples from herds were collected and sent to the local commercial processing plant in Majes for detection of antibodies against BVDV by indirect ELISA test. In the second phase, 286 blood samples from 57 were collected strong positive (Optical Density [OD] ≥ 0.900) for the detection of herds antibodies against BVDV and in PI animals by the indirect and capture ELISAs respectively. In …

Alternative Targets For The Treatment Of Stroke, Craig T. Ajmo Jr.

USF Tampa Graduate Theses and Dissertations

Stroke is cerebrovascular injury that has been reported to be the third leading cause of death and the first leading cause of disability in the world (W. H.O. 2007). Currently, there is only one FDA approved treatment for stroke which is recombinant tissue plasminogen activator. This treatment has a narrow therapeutic window of three hours after ischemic stroke and can adversely cause the production of oxygen free radicals and intracranial hemorrhage. These limitations result in only 2-3% of all stroke victims as being candidates for this therapy as many patients do not arrive at the hospital in time to receive …

Alcohol Slows Interhemispheric Transmission, Increases The Flash-Lag Effect, And Prolongs Masking: Evidence For A Slowing Of Neural Processing And Transmission., Sarah A Khan, Brian Timney

Brain and Mind Institute Researchers' Publications

While the alcohol literature is extensive, relatively little addresses the relationship between physiological effects and behavioural changes. Using the visual system as a model, we examined alcohol's influence on neural temporal processing as a potential means for alcohol's effects. We did this by using tasks that provided a measure of processing speed: Poffenberger paradigm, flash-lag, and backward masking. After moderate alcohol, participants showed longer interhemispheric transmission times, larger flash-lags, and prolonged masking. Our data are consistent with the view that alcohol slows neural processing, and provide support for a reduction in processing efficiency underlying alcohol-induced changes in temporal visual processing.

Electromagnetic Differences In The Brain During Memory Retrieval, Warren Scott Merrifield

Loma Linda University Electronic Theses, Dissertations & Projects

The primary objectives for this experiment were to analyze the neuroanatomical correlates of autobiographical, episodic and semantic memory, use a different paradigm to promote episodic memory retrieval, and employ a different analysis technique to understand retrieval processes. Autobiographical and episodic memories are personal memories from the past. Autobiographical is more general (e.g. a street name of a house growing up) and episodic is more specific to time (e.g. 13th birthday party that took place on a street). For autobiographical and episodic memory retrieval operations, there is no general consensus as to the localization of function, but bilateral activation of the …

The Neural Correlates Of Inhibitory Control In Preschool Children: Go/No-Go Task Demands Influence Erp Amplitude And Latency, S. A. Wiebe, D. J. Carroll, S. Raber, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

No abstract provided.

Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of senile dementia in the US and worldwide but the causes of its pathogenesis are currently unknown. In this study, we examined two processes that have been implicated in the early stages of AD and other forms of neurodegeneration, iron dysregulation and inflammation, both of which can promote the increased production of amyloid precursor protein (APP). We have measured different pools of brain iron in transgenic iron regulatory protein 2 knockout (IRP2-/-) mice in the early stages of neurodegeneration and in affected brain regions from AD patients at different stages of the …

Relevance To Self: A Brief Review And Framework Of Neural Systems Underlying Appraisal, Taylor W. Schmitz, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

We argue that many similar findings observed in cognitive, affective, and social neuroimaging research may compose larger processes central to generating self-relevance. In support of this, recent findings from these research domains were reviewed to identify common systemic activation patterns. Superimposition of these patterns revealed evidence for large-scale supramodal processes, which are argued to mediate appraisal of self-relevant content irrespective of specific stimulus types (e.g. words, pictures) and task domains (e.g. induction of reward, fear, pain, etc.). Furthermore, we distinguish between two top-down sub-systems involved in appraisal of self-relevance, one that orients pre-attentive biasing information (e.g. anticipatory or mnemonic) to …

Restraint-Induced Corticosterone Secretion And Hypothalamic Crh Mrna Expression Are Augmented During Acute Withdrawal From Chronic Cocaine Administration, John R. Mantsch, Sarah Taves, Tayyiba Khan, Eric S. Katz, Tanveer Sajan, Lee C. Tang, William E. Cullinan, Dana R. Ziegler

Biomedical Sciences Faculty Research and Publications

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus …

Perceptual Functions Of Perirhinal Cortex In Rats: Zero-Delay Object Recognition And Simultaneous Oddity Discriminations., Susan J Bartko, Boyer D Winters, Rosemary A Cowell, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

The perirhinal cortex (PRh) is widely accepted as having an important role in object recognition memory in humans and animals. Contrary to claims that PRh mediates declarative memory exclusively, previous evidence suggests that PRh has a role in the perceptual processing of complex objects. In the present study, we conducted an examination of the possible role of PRh in perceptual function in rats. We examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus postrhinal cortices) in the rat would cause deficits in a zero-delay object-recognition task and a simultaneous oddity discrimination task. Both of these tasks measured spontaneous …

Genetic Factors In Preschool Executive Control: Relations Between Serotonin Genotype, Working Memory, And Set Shifting, S. A. Wiebe, M. Y. Chang, A. R. Johnson, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

No abstract provided.

Retroviral Vector And Cell-Based Assay For Measuring The Mutation Rate Of Retroviruses Employing Same, Dawn P. Wooley, Kelly Jo Huang

Neuroscience, Cell Biology & Physiology Faculty Publications

Lentiviral-based retrovirus vectors and an in vivo mutation rate assay employing them. More particularly, an assay for directly determining the in vivo mutation rate of HIV-1.

Is Gene Therapy A Good Therapeutic Approach For Hiv-Positive Patients?, Jai G. Marathe, Dawn P. Wooley

Neuroscience, Cell Biology & Physiology Faculty Publications

Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and …

Genes And Behavior In Preschool Children: The Relation Between Dopamine Genotype And Latent Executive Control, S. A. Wiebe, M. J. Moehr, A. R. Johnson, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Objective: Dopaminergic neurotransmission is implicated in the executive control of cognition and behavior (Braver & Cohen, 2000). Presence or absence of particular dopamine gene alleles relates to executive control performance (Casey, 2002; Roesch-Ely, 2005) and to attention problems and ADHD (Durston, 2005; Schmidt, 2001). The present study examined the relation between dopamine genotype and executive control in normally-developing preschool children. Participants and Methods: The sample included 133 children (66 girls; mean age 4 years, range 2;2-6 years). Children completed a battery of executive control tasks, and were genotyped for 4 dopamine genes: the dopamine receptors DRD2 and DRD4, the dopamine …

Β-N-Methylamino-L-Alanine Enhances Neurotoxicity Through Multiple Mechanisms, Doug Lobner, Peachy Mae T. Piana, Abed K. Salous, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The idea that the environmental toxin β-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 μM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and …

Anosognosia In Mild Cognitive Impairment: Relationship To Activation Of Cortical Midline Structures Involved In Self-Appraisal, Michele L. Ries, Britta M. Jabbar, Taylor W. Schmitz, Mehul A. Trivedi, Carey E. Gleason, Cynthia M. Carlsson, Howard A. Rowley, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI …

Cognition As An Outcome Measure In Schizophrenia, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Atypical Antipsychotics And Cognitive Enhancement In Schizophrenia: The Current Status, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Adenoviral Mediated Gene Transfer Into The Dog Brain In Vivo, Marianela Candolfi, Kurt Kroeger, Elizabeth Pluhar, Chunyan Liu, Carlos Barcia, Josee Bergeron, Mariana Puntel, James Curtin, Elizabeth Mcniel, Andrew Freese, John Ohlfest, Peter Moore, William Kuoy, Pedro Lowenstein, Maria Castro

Articles

OBJECTIVE: Glioblastoma multiforme (GBM) is a devastating brain tumor for which there is no cure. Adenoviral-mediated transfer of conditional cytotoxic (herpes simplex virus [HSV] 1-derived thymidine kinase [TK]) and immunostimulatory (Fms-like tyrosine kinase 3 ligand [Flt3L]) transgenes elicited immune-mediated long-term survival in a syngeneic intracranial GBM model in rodents. However, the lack of a large GBM animal model makes it difficult to predict the outcome of therapies in humans. Dogs develop spontaneous GBM that closely resemble the human disease; therefore, they constitute an excellent large animal model. We assayed the transduction efficiency of adenoviral vectors (Ads) encoding beta-galactosidase (betaGal), TK, …