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Full-Text Articles in Medicine and Health Sciences

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu Nov 2017

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu

Russell W. Brown

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and …


Epigenetic Suppression Of Hippocampal Calbindin-D28k By Δfosb Drives Seizure-Related Cognitive Deficits., Jason C. You, Kavitha Muralidharan, Jin W. Park, Iraklis Petrof, Mark S. Pyfer, Brian F. Corbett, John J. Lafrancois, Yi Zheng, Xiaohong Zhang, Carrie A. Mohila, Daniel Yoshor, Robert A. Rissman, Eric J. Nestler, Helen E. Scharfman, Jeannie Chin Nov 2017

Epigenetic Suppression Of Hippocampal Calbindin-D28k By Δfosb Drives Seizure-Related Cognitive Deficits., Jason C. You, Kavitha Muralidharan, Jin W. Park, Iraklis Petrof, Mark S. Pyfer, Brian F. Corbett, John J. Lafrancois, Yi Zheng, Xiaohong Zhang, Carrie A. Mohila, Daniel Yoshor, Robert A. Rissman, Eric J. Nestler, Helen E. Scharfman, Jeannie Chin

Department of Neuroscience Faculty Papers

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer's disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. …


Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka Sep 2017

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …


Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K(+) Channel Dysfunction In Drg Neurons., Benjamin M. Zemel, Tanziyah Muqeem, Eric V. Brown, Miguel Goulão, Mark W Urban, Stephen R. Tymanskyj, Angelo C. Lepore, Manuel Covarrubias Aug 2017

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K(+) Channel Dysfunction In Drg Neurons., Benjamin M. Zemel, Tanziyah Muqeem, Eric V. Brown, Miguel Goulão, Mark W Urban, Stephen R. Tymanskyj, Angelo C. Lepore, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar …


Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai Jul 2017

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …


Targeting Antioxidant Enzyme Expression As A Therapeutic Strategy For Ischemic Stroke, Stephanie M. Davis, Keith R. Pennypacker Jul 2017

Targeting Antioxidant Enzyme Expression As A Therapeutic Strategy For Ischemic Stroke, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

During ischemic stroke, neurons and glia are subjected to damage during the acute and neuroinflammatory phases of injury. Production of reactive oxygen species (ROS) from calcium dysregulation in neural cells and the invasion of activated immune cells are responsible for stroke-induced neurodegeneration. Scientists have failed thus far to identify antioxidant-based drugs that can enhance neural cell survival and improve recovery after stroke. However, several groups have demonstrated success in protecting against stroke by increasing expression of antioxidant enzymes in neural cells. These enzymes, which include but are not limited to enzymes in the glutathione peroxidase, catalase, and superoxide dismutase families, …


Sensory Processing In Autism Spectrum Disorders And Fragile X Syndrome-From The Clinic To Animal Models., D Sinclair, B Oranje, K A Razak, S J Siegel, S Schmid May 2017

Sensory Processing In Autism Spectrum Disorders And Fragile X Syndrome-From The Clinic To Animal Models., D Sinclair, B Oranje, K A Razak, S J Siegel, S Schmid

Brain and Mind Institute Researchers' Publications

Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and …


Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats., Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O Poulter, Susanne Schmid Apr 2017

Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats., Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O Poulter, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, …


Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma Feb 2017

Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma

Department of Neuroscience Faculty Papers

Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in …


Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette Feb 2017

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …


Neurovascular Astrocyte Degeneration In The Hyperhomocysteinemia Model Of Vascular Cognitive Impairment And Dementia (Vcid), Tiffany L. Sudduth, Erica M. Weekman, Brittani Rae Price, Jennifer L. Gooch, Abigail E. Woolums, Christopher M. Norris, Donna M. Wilcock Jan 2017

Neurovascular Astrocyte Degeneration In The Hyperhomocysteinemia Model Of Vascular Cognitive Impairment And Dementia (Vcid), Tiffany L. Sudduth, Erica M. Weekman, Brittani Rae Price, Jennifer L. Gooch, Abigail E. Woolums, Christopher M. Norris, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer’s disease (AD) and is a frequent co-morbidity with AD. Despite its prevalence, little is known about the molecular mechanisms underlying the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end-feet almost completely surround intraparenchymal blood vessels in the brain and express a variety of channels and markers indicative of their specialized functions in the maintenance of ionic and osmotic homeostasis and gliovascular signaling. These functions are mediated by end-foot enrichment of the aquaporin 4 water channel (AQP4), the inward rectifying potassium channel Kir4.1 and the calcium-dependent …


Hippocampal Neurogenesis And Volume In Migrating And Wintering Semipalmated Sandpipers (Calidris Pusilla)., Nara Gyzely De Morais Magalhães, Cristovam Guerreiro Diniz, Daniel Guerreiro Diniz, Ediely Pereira Henrique, Patrick Douglas Corrêa Pereira, Isis Ananda Matos Moraes, Mauro André Damasceno De Melo, David Francis Sherry, Cristovam Wanderley Picanço Diniz Jan 2017

Hippocampal Neurogenesis And Volume In Migrating And Wintering Semipalmated Sandpipers (Calidris Pusilla)., Nara Gyzely De Morais Magalhães, Cristovam Guerreiro Diniz, Daniel Guerreiro Diniz, Ediely Pereira Henrique, Patrick Douglas Corrêa Pereira, Isis Ananda Matos Moraes, Mauro André Damasceno De Melo, David Francis Sherry, Cristovam Wanderley Picanço Diniz

Brain and Mind Institute Researchers' Publications

Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla) is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information …


Proteome Analysis Of Bronchoalveolar Lavage From Calves Infected With Bovine Respiratory Syncytial Virus-Insights In Pathogenesis And Perspectives For New Treatments., Sara Hägglund, Krister Blodörn, Katarina Näslund, Karin Vargmar, Sara Bergström Lind, Jia Mi, Mariluz Araínga, Sabine Riffault, Geraldine Taylor, John Pringle, Jean François Valarcher Jan 2017

Proteome Analysis Of Bronchoalveolar Lavage From Calves Infected With Bovine Respiratory Syncytial Virus-Insights In Pathogenesis And Perspectives For New Treatments., Sara Hägglund, Krister Blodörn, Katarina Näslund, Karin Vargmar, Sara Bergström Lind, Jia Mi, Mariluz Araínga, Sabine Riffault, Geraldine Taylor, John Pringle, Jean François Valarcher

Journal Articles: Pharmacology & Experimental Neuroscience

Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected calves was analysed by tandem mass spectrometry. Proteins were semi-quantified and protein expression was validated by immunoblotting. Correlations between selected proteins and pathology, clinical signs and virus shedding were investigated. Calves with BRSV-induced disease had increased total protein concentrations and a decreased …


Are There Place Cells In The Avian Hippocampus?, David F Sherry, Stephanie L Grella, Mélanie F Guigueno, David J White, Diano F Marrone Jan 2017

Are There Place Cells In The Avian Hippocampus?, David F Sherry, Stephanie L Grella, Mélanie F Guigueno, David J White, Diano F Marrone

Brain and Mind Institute Researchers' Publications

Birds possess a hippocampus that serves many of the same spatial and mnemonic functions as the mammalian hippocampus but achieves these outcomes with a dramatically different neuroanatomical organization. The properties of spatially responsive neurons in birds and mammals are also different. Much of the contemporary interest in the role of the mammalian hippocampus in spatial representation dates to the discovery of place cells in the rat hippocampus. Since that time, cells that respond to head direction and cells that encode a grid-like representation of space have been described in the rat brain. Research with homing pigeons has discovered hippocampal cells, …


Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti Jan 2017

Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two apparently distinct neurodegenerative diseases, the former characterized by selective loss of motor neurons in the brain and spinal cord and the latter characterized by selective atrophy of frontal and temporal lobes. Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene …


Harnessing The Power Of Cell Transplantation To Target Respiratory Dysfunction Following Spinal Cord Injury., Brittany A. Charsar, Mark W. Urban, Angelo C. Lepore Jan 2017

Harnessing The Power Of Cell Transplantation To Target Respiratory Dysfunction Following Spinal Cord Injury., Brittany A. Charsar, Mark W. Urban, Angelo C. Lepore

Department of Neuroscience Faculty Papers

The therapeutic benefit of cell transplantation has been assessed in a host of central nervous system (CNS) diseases, including disorders of the spinal cord such as traumatic spinal cord injury (SCI). The promise of cell transplantation to preserve and/or restore normal function can be aimed at a variety of therapeutic mechanisms, including replacement of lost or damaged CNS cell types, promotion of axonal regeneration or sprouting, neuroprotection, immune response modulation, and delivery of gene products such as neurotrophic factors, amongst other possibilities. Despite significant work in the field of transplantation in models of SCI, limited attention has been directed at …