Medical Neurobiology Commons^™

Towards Objectively Quantifying Sensory Hypersensitivity: A Pilot Study Of The “Ariana Effect.”, Vassilis N. Panagopoulos, Deanna J. Greene, Meghan C. Campbell, Kevin J. Black

Kevin J. Black, MD

Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH.

Methods. Nineteen ambulatory adult volunteers with varying scores …

Spatial Reorganization Of Putaminal Dopamine D2-Like Receptors In Cranial And Hand Dystonia, Kevin J. Black, Abraham Z. Snyder, Jonathan W. Mink, Veeral N. Tolia, Fredy J. Revilla, Stephen M. Moerlein, Joel S. Perlmutter

Kevin J. Black, MD

No abstract provided.

Exploring Volatile General Anesthetic Binding To A Closed Membrane-Bound Bacterial Voltage-Gated Sodium Channel Via Computation., S G Raju, Annika F Barber, David N Lebard, Michael L Klein, Vincenzo Carnevale

Department of Neuroscience Faculty Papers

Despite the clinical ubiquity of anesthesia, the molecular basis of anesthetic action is poorly understood. Amongst the many molecular targets proposed to contribute to anesthetic effects, the voltage gated sodium channels (VGSCs) should also be considered relevant, as they have been shown to be sensitive to all general anesthetics tested thus far. However, binding sites for VGSCs have not been identified. Moreover, the mechanism of inhibition is still largely unknown. The recently reported atomic structures of several members of the bacterial VGSC family offer the opportunity to shed light on the mechanism of action of anesthetics on these important ion …

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

Kevin M Rice

Background: Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and …

Cannabis And Psychosis: Transition To Psychosis, Amresh Srivastava, Kristen , Terpstra, Yves Bureau

Amresh Srivastava

Cannabis has been implicated as a risk factor for the development of schizophrenia, however, but the pathway of cannabis causing psychosis is not well understood. It appears that cannabis does not cause any structural changes per say but deficits in areas of the brain responsible for memory and emotion do show some changes. Recent studies suggest that cannabinoids such as CB1 have a pharmacological profile similar to that of atypical antipsychotic drugs. This mechanisms may involve dopamine, GABA, and glutamate neurotransmission; It is still not known if these changes are transitory or permanent, and whether or not they contribute to …

The Effect Of Nerve Growth Factor (Ngf) Incorporation Into Swine Intestinal Submucosa (Sis) Suture Material On The Healing Process In Gastrocnemius Muscle, Nicole K. Alexander

PCOM Biomedical Studies Student Scholarship

The repair of gastrocnemius muscle incisions were evaluated histologically in a rat model. Comparisons were made between carbon dioxide laser and scalpel incisions closed with sutures prepared from Swine Intestinal Submucosa (SIS) with and without added Nerve Growth Factor. This study was conducted in conjunction with two other studies, one comparing epidermal repair and the other comparing kinesthetic changes post-operatively in the same animal model. Thirty-five days post-surgery the animals were euthanized and an area of muscular tissue encompassing the operative site was excised and evaluated microscopically for the following: presence of macrophages, integrity of the muscle, leukocytes present within …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …

Celiac Disease And Neurological Symptoms, Lauren V. Cook

Senior Honors Theses

New research has revealed that Celiac disease, an autoimmune illness affecting the small intestine, has more ties with neurological side effects than once was thought. The classic and most well known presentation of Celiac disease is gastrointestinal, including symptoms such as abdominal pains, nausea, diarrhea, and flatulence. Researchers have more recently found a correlation between Celiac disease and neurological illnesses such as epilepsy, depression, dementia, and ADHD. Physician awareness of the disease and the neurological side of the illness should be heightened in order for patients to receive earlier diagnosis and a better quality of life. Because of the difficulty …

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and …

Human Synaptic Plasticity Gene Expression Profile And Dendritic Spine Density Changes In Hiv-Infected Human Cns Cells: Role In Hiv-Associated Neurocognitive Disorders (Hand), Venakata Subba Rao Alturi, Sudheesh P. Kanthikeel, Pichili V.B. Reddy, Adriana Yndart, Madhavan P.N. Nair

HWCOM Faculty Publications

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated …

Microglial Disruption In Young Mice With Early Chronic Exposure To Lead, Christina Sobin, Mayra Flores Montoya, Natali Parisi, Tanner Schaub, Miguel Cervantes, Rodrigo Armijos

Christina Sobin, Ph.D.

The mechanisms by which early chronic lead (Pb) exposure alters brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) …

The P38Α Mapk Regulates Microglial Responsiveness To Diffuse Traumatic Brain Injury, Adam D. Bachstetter, Rachel K. Rowe, Machi Kaneko, Danielle Goulding, Jonathan Lifshitz, Linda J Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Neuropathology after traumatic brain injury (TBI) is the result of both the immediate impact injury and secondary injury mechanisms. Unresolved post-traumatic glial activation is a secondary injury mechanism that contributes to a chronic state of neuroinflammation in both animal models of TBI and human head injury patients. We recently demonstrated, using in vitro models, that p38α MAPK signaling in microglia is a key event in promoting cytokine production in response to diverse disease-relevant stressors and subsequent inflammatory neuronal dysfunction. From these findings, we hypothesized that the p38α signaling pathway in microglia could be contributing to the secondary neuropathologic sequelae after …

Deficiency In P38Β Mapk Fails To Inhibit Cytokine Production Or Protect Neurons Against Inflammatory Insult In In Vitro And In Vivo Mouse Models, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The p38 MAPK pathway plays a key role in regulating the production of proinflammatory cytokines, such as TNFα and IL-1β, in peripheral inflammatory disorders. There are four major isoforms of p38 MAPK (p38α, β, δ, γ), with p38α and p38β the targets of most p38 MAPK inhibitor drugs. Our previous studies demonstrated that the p38α MAPK isoform is an important contributor to stressor-induced proinflammatory cytokine up-regulation and neurotoxicity in the brain. However, the potential role of the p38β MAPK isoform in CNS proinflammatory cytokine overproduction and neurotoxicity is poorly understood. In the current studies, we used primary microglia from wild …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller

Dartmouth Scholarship

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright

Dartmouth Scholarship

Background: Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III).

Methods: NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

Eric Blough

Background: Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Glutamate Dysregulation And Hippocampal Dysfunction In Epileptogenesis, Seth R. Batten

Theses and Dissertations--Medical Sciences

Epileptogenesis is the complex process of the brain developing epileptic acitivity. Due to the role of glutamate and the hippocampus in synaptic plasticity a dysregulation in glutamate neurotransmission and hippocampal dysfunction are implicated in the process of epileptogenesis. However, the exact causal factors that promote epileptogenesis are unknown.

We study presynaptic proteins that regulate glutamate neurotransmission and their role in epileptogenesis. The presynaptic protein, tomosyn, is believed to be a negative regulator of glutamate neurotransmission; however, no one has studied the effects of this protein on glutamate transmission in vivo. Furthermore, evidence suggests that mice lacking tomosyn have a …