Neurosciences Commons^™

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Stressor- And Corticotropin Releasing Factor-Induced Reinstatement And Active Stress-Related Behavioral Responses Are Augmented Following Long-Access Cocaine Self-Administration By Rats, John R. Mantsch, David A. Baker, David M. Francis, Eric S. Katz, Michael A. Hoks, Joseph P. Serge

Biomedical Sciences Faculty Research and Publications

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness.

Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA).

Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and …

Searching For The Majority: Algorithms Of Voluntary Control, Jin Fan, Kevin G. Guise, Xun Liu, Hongbin Wang

Faculty, Staff and Student Publications

Voluntary control of information processing is crucial to allocate resources and prioritize the processes that are most important under a given situation; the algorithms underlying such control, however, are often not clear. We investigated possible algorithms of control for the performance of the majority function, in which participants searched for and identified one of two alternative categories (left or right pointing arrows) as composing the majority in each stimulus set. We manipulated the amount (set size of 1, 3, and 5) and content (ratio of left and right pointing arrows within a set) of the inputs to test competing hypotheses …

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 …

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 …

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 …

Neuromechanics Of Multifunctionality During Rejection In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

How are the same muscles and neurons used to generate qualitatively different behaviors? We studied this question by analyzing the biomechanical and neural mechanisms of rejection responses in the marine mollusk Aplysia californica and compared these mechanisms with those used to generate swallowing responses (Ye et al., 2006). During rejection, the central grasper of the feeding structure closes to push inedible food out of the buccal cavity. This contrasts with swallowing, during which the grasper is open as it moves toward the jaws (protracts). We examined how the shape change of the grasper during rejection mechanically reconfigured the surrounding musculature. …

Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley

UNLV Magazine

No abstract provided.

Neuromechanics Of Coordination During Swallowing In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

Bernstein (1967) hypothesized that preparation of the periphery was crucial for correct responses to motor output. To test this hypothesis in a behaving animal, we examined the roles of two identified motor neurons, B7 and B8, which contribute to feeding behavior in the marine mollusk Aplysia californica. Neuron B7 innervates a hinge muscle and has no overt behavioral effect during smaller-amplitude (type A) swallows, because the hinge muscle is too short to exert force. Neuron B8 activates a muscle (I4) that acts solely to grasp material during type A swallows. During larger-amplitude (type B) swallows, the behavioral actions of both …

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

A New Interpretation Of The Drug Levodopa In The Treatment Of Parkinson's Disease, Joanne T. Vannah

Graduate Masters Theses

An argument for levodopa induced dyskinesias (LID) as an expression of long term potentiation (LTP) in the striatum is presented. Normally, with an intact nigrostriatal dopamine (DA) input, long term depression (LTD) is expressed in the striatum, however, striatal LTD is lost following DA denervation and chronic levodopa treatment. It is possible that these changes in synaptic efficacy are due to two other chemical modulators, achetylcholine (ACh) and glutamate, which in turn leads to the induction of striatal LTP. ACh and glutamate may produce these changes in motor behavior by affecting the striosomal pathway in addition to their effect on …

Visual Enhancing Of Tactile Perception In The Posterior Parietal Cortex, Tony Ro, Ruth Wallace, Judith Hagedorn, Alessandro Farnè, Elizabeth Pienkos

Publications and Research

The visual modality typically dominates over our other senses. Here we show that after inducing an extreme conflict in the left hand between vision of touch (present) and the feeling of touch (absent), sensitivity to touch increases for several minutes after the conflict. Transcranial magnetic stimulation of the posterior parietal cortex after this conflict not only eliminated the enduring visual enhancement of touch, but also impaired normal tactile perception. This latter finding demonstrates a direct role of the parietal lobe in modulating tactile perception as a result of the conflict between these senses. These results provide evidence for visual-to-tactile perceptual …

Residency Program At Michael E Debakey Department Of Surgery, Baylor College Of Medicine, F Charles Brunicardi

Faculty, Staff and Students Publications

No abstract provided.

Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths Via Rhog-Mediated Mechanisms, Victor May, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during evelopment. In mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio, broadly expressed throughout the body, is expressed at a lower level in the nervous system. To evaluate the role of Kalirin in fiber initiation and outgrowth, we microinjected cultured sympathetic neurons with vectors encoding Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense oligonucleotides blocked the …

Ipsilesional Biases In Saccades But Not Perception After Lesions Of The Human Inferior Parietal Lobule, Tony Ro, Chris Rorden, Jon Driver, Robert Rafal

Publications and Research

We examined the effects of chronic unilateral lesions to either the inferior parietal lobe, or to the dorsolateral prefrontal cortex including the frontal eye fields (FEFs), upon human visual perception and saccades in temporal-order-judgment (TOJ) tasks. Two visual events were presented on each trial, one in each hemifield at various stimulus onset asynchronies (SOAs). In the saccade task, patients moved their eyes to whichever stimulus attracted gaze first. In the perceptual-manual task, they pressed a button to indicate which stimulus was perceived first. Frontal patients showed appropriate TOJs for visual targets in both tasks. Parietal patients showed appropriate TOJs in …

Neuromotor And Cognitive Development In Children With Cerebral Palsy In Relation To Neural Plasticity, Vaniecea Pollard

McCabe Thesis Collection

Infants with neurological disabilities, such as cerebral palsy (CP) and Down syndrome (DS), show severe delays in motor and cognitive development relative to chronological age. Involvement of neural plasticity as a treatment of such neurological disorders is increasingly being seen. Previous studies have found that interventions involving sensory linked motor performance have been critical in facilitating motor improvement. The purpose of this study was to compare self-initiated mobility in children with CP and DS. Three infants, ages 8, 9, and 22 months, with diagnoses of no CP, DS, and CP respectively, participated in the study. The infants were videotaped in …

Direct Demonstration Of Retroviral Recombination In A Rhesus Monkey, Dawn P. Wooley, Randall A. Smith, Susan Czajak, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Recombination may be an important mechanism for increasing variation in retroviral populations. Retroviral recombination has been demonstrated in tissue culture systems by artificially creating doubly infected cells. Evidence for retroviral recombination in vivo is indirect and is based principally on the identification of apparently mosaic human immunodeficiency virus type 1 genomes from phylogenetic analyses of viral sequences. We infected a rhesus monkey with two different molecularly cloned strains of simian immunodeficiency virus. One strain of virus had a deletion in vpx and vpr, and the other strain had a deletion in nef. Each strain on its own induced low virus …

Transcranial Magnetic Stimulation Of The Prefrontal Cortex Delays Contralateral Endogenous Saccades, Tony Ro, Avishai Henik, Liana Machado, Robert D. Rafal

Publications and Research

The contributions of the superior prefrontal cortex (SPFC) and the superior parietal lobule (SPL) in generating voluntary endogenous and reflexive visually guided saccades were investigated using transcranial magnetic stimulation (TMS). Subjects made choice saccades to the left or right visual field in response to a central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go signal) that were presented along with a single TMS pulse at varying temporal intervals. TMS over the SPFC increased latencies for saccades made in response to an endogenous go signal toward the contralateral hemifield. No effects were observed when the go signal was exogenous …

Modulation Of Neutrophil Functions By Neurotransmitters Implicated In Stress, Chok Ping Wan

Loma Linda University Electronic Theses, Dissertations & Projects

Stress has long been implicated in immune modulation. People under chronic stress have no change in the circulating basal levels of catecholamines while plasma levels of neuropeptide Y (NPY) are significantly increased. Sympathetic nerve fibers with NPY have been found to innervate immune organs. It was hypothesized that NPY might be a mediator in immune modulation in people under chronic stress. Human neutrophils were used as a model to study the effects of NPY alone or together with norepinephrine on the immune system. We now report that NPY modulates oxidative burst (OB) triggered by zymosan in human neutrophils while it …

Effects Of Natural Sequence Variation On Recognition By Monoclonal Antibodies Neutralize Simian Immunodeficiency Virus Infectivity, Weon Sang Choi, Catherine Collignon, Clotilde Thiriart, Dawn P. Wooley, E. J. Scott, Karen A. Kent, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

The determinants of immune recognition by five monoclonal antibodies (KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus infectivity were analyzed. These five neutralizing monoclonal antibodies were generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus recombinant vector. All five recognize conformational or discontinuous epitopes and require native antigen for optimal recognition. These monoclonal antibodies also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural variants of SIVmac239, 1-12 and 8-22, which evolved during the course of persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which …

High Rates Of Frameshift Mutations Within Homo-Oligomeric Runs During A Single Cycle Of Retroviral Replication, Dawn P. Wooley, H. M. Temin

Neuroscience, Cell Biology & Physiology Faculty Publications

Homo-oligomeric runs were inserted into a spleen necrosis virus-based retrovirus vector to determine the nature and rate of mutations within runs of 10 to 12 identical nucleotides during a single replication cycle. Clones of helper cells containing integrated copies of retroviral vectors were used to produce virus for infection of target (nonhelper) cells. Proviral sequences from target cell clones were compared with proviral sequences from helper cell clones to study mutations that occurred during a single cycle of replication. In addition to the internal region spanning the homo-oligomeric inserts, a naturally occurring run of 10 T's in the long terminal …

Simian Immunodeficiency Virus Mutants Resistant To Serum Neutralization Arise During Persistent Infection Of Rhesus Monkeys, Dawn P. Wooley, Catherine Collignon, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

We previously described the pattern of sequence variation in gp120 following persistent infection of rhesus monkeys with the pathogenic simian immunodeficiency virus SIVmac239 molecular clone (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843, 1991). Sequence changes were confined largely to five variable regions (V1 to V5), four of which correspond to human immunodeficiency virus type 1 (HIV-1) gp120 variable regions. Remarkably, 182 of 186 nucleotide substitutions that were documented in these variable regions resulted in amino acid changes. This is an extremely nonrandom pattern, which suggests selective pressure driving amino acid changes in discrete variable domains. In the present study, …

Strain-Specific Neutralizing Determinant In The Transmembrane Protein Of Simian Immunodeficiency Virus, Toshiaki Kodama, Dawn P. Wooley, Daniel P. Silva, Fulvia Dimarzo Veronese, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Monoclonal antibody SF8/5E11, which recognizes the transmembrane protein (TMP) of simian immunodeficiency virus of macaque monkeys (SIVmac), displayed strict strain specificity. It reacted with cloned and uncloned SIVmac251 but not with cloned SIVmac142 and SIVmac239 on immunoblots. This monoclonal antibody neutralized infection by cloned, cell-free SIVmac251 and inhibited formation of syncytia by cloned SIVmac251-infected cells; these activities were specific to cloned SIVmac251 and did not occur with the other viruses. Site-specific mutagenesis was used to show that TMP amino acids 106 to 110 (Asp-Trp-Asn-Asn-Asp) determined the strain specificity of the monoclonal antibody. This strain-specific neutralizing determinant is located within a …

Selection Of Genetic Variants Of Simian Immunodeficiency Virus In Persistently Infected Rhesus Monkeys, Dawn P. Wooley, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Genetic and antigenic variation may be one means by which lentiviruses that cause AIDS avoid elimination by host immune responses. Genetic variation in the envelope gene (env) was studied by comparing the nucleotide sequences of 27 clones obtained from two rhesus monkeys infected with molecularly cloned simian immunodeficiency virus. All 27 clones differed from each other and differed from the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide substitutions were shown to accumulate with time at an average rate of 8.5 per 1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions (81%) resulted in …

Significance Of Premature Stop Codons In Env Of Simian Immunodeficiency Virus, Toshiaki Kodama, Dawn P. Wooley, Yathirajulu M. Naidu, Harry W. Kestler Iii, Muthiah D. Daniel, Yen Li, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

The location of the translational termination codon for the transmembrane protein (TMP) varies in three infectious molecular clones of simian immunodeficiency virus from macaques (SIV_mac). The SIV_mac251 and SIV_mac142 infectious clones have premature stop signals that differ in location by one codon; transfection of these DNAs into human HUT-78 cells yielded virus with a truncated TMP (28 to 30 kilodaltons [kDa]). The SIV_mac239 infectious clone does not have a premature stop codon in its TMP-coding region. Transfection of HUT-78 cells with this clone initially yielded virus with a full-length TMP (41 kDa). …

An Identified Histaminergic Neuron Can Modulate The Outputs Of Buccal-Cerebral Interneurons In Aplysia Via Presynaptic Inhibition, Hillel J. Chiel

Faculty Scholarship

We have identified 2 buccal-cerebral interneurons (BCIs), B17 and B18, that appear to be involved in the coordination of feeding behavior in Aplysia. The BCIs have their cell bodies in the buccal ganglion, but send axons to the cerebral ganglion via the cerebral-buccal connectives. The BCIs appear to make monosynaptic connections with neurons in the cerebral ganglion that modulate extrinsic muscles involved in feeding behavior. B17 and B18 are activated antiphasically during a motor program induced by stimulating the esophageal nerve and appear to 'read out' different phases of the buccal program to different cells in the cerebral ganglion. B17 …

Activity Of An Identified Histaminergic Neuron, And Its Possible Role In Arousal Of Feeding Behavior In Semi-Intact Aplysia, Hillel J. Chiel

Faculty Scholarship

The possible functions of histaminergic neuron C2 were studied in an isolated head preparation from which it was possible to obtain intracellular recordings while the buccal mass exhibited feeding-like responses. Application of food to the lips of the isolated head preparation elicited rhythmic buccal movements that appeared to be ingestion responses, since they moved seaweed into the buccal cavity and towards the esophagus, and their frequency and regularity was similar to the ingestion responses studied in a group of intact animals. The ingestion responses of the buccal mass consisted of 2 main phases of movement of the radula from a …

Sensory Function And Gating Of Histaminergic Neuron C2 In Aplysia, Hillel J. Chiel

Faculty Scholarship

This paper explores the possible sensory function of the identified histaminergic neuron C2. Mechanical stimulation of a narrow region around the mouth of the animal (perioral zone) elicits brief depolarizing potentials in C2. Extracellular recordings from the peripheral axons of C2 indicate that the depolarizing potentials are due to action potentials that are conveyed from the periphery but do not invade the cell body, since they fail at a region with a low safety factor within the cerebral ganglion. These blocked axonal spikes (A- spikes) function as if they were excitatory synaptic inputs to C2, since the synaptic output of …

An Identified Histaminergic Neuron Modulates Feeding Motor Circuitry In Aplysia, Hillel J. Chiel

Faculty Scholarship

An identified histaminergic neuron, C2, in the marine mollusk Aplysia is a complex mechanoafferent which appears to contribute to the maintenance of food arousal by means of its synaptic connections to the metacerebral cell (MCC). Because C2 also has extensive synaptic outputs to neurons other than the MCC, we studied its possible motor functions. We identified several synaptic followers of C2 and found that some were excitatory motor neurons for extrinsic muscles of the buccal mass, while others were modulatory motor neurons that inhibited contractions. In addition, we found that these neurons and other synaptic followers of C2 received powerful …

Cardioregulatory Role Of The Abdominal Ganglion Of Aplysia Californica, George Maeda

Loma Linda University Electronic Theses, Dissertations & Projects

An isolated heart-abdominal ganglion preparation of this mollusc was developed and used to study the cardioregulatory function of the ganglion and nerves. The heart was perfused with artificial sea water through an atrial cannula and the gastro-esophageal artery was catheterized for blood pressure monitoring. The presence and cardioregulatory effects of axons in the nerves was investigated by electrical stimulation. Fine-tipped glass microelectrodes inserted into ganglionic neurons were used to determine the relationship between the neuronal and cardiac activities.

The principal results are listed below.

1. Primarily inhibitory responses are obtained from both right and left connective stimulation, with some evidence for …