Neurosciences Commons^™

Isolation Of Cerebral Capillaries From Fresh Human Brain Tissue, Anika M. S. Hartz, Julia A. Schulz, Brent S. Sokola, Stephanie E. Edelmann, Andrew N. Shen, Ralf G. Rempe, Yu Zhong, Nader El Seblani, Bjoern Bauer

Sanders-Brown Center on Aging Faculty Publications

Understanding blood-brain barrier function under physiological and pathophysiological conditions is critical for the development of new therapeutic strategies that hold the promise to enhance brain drug delivery, improve brain protection, and treat brain disorders. However, studying the human blood-brain barrier function is challenging. Thus, there is a critical need for appropriate models. In this regard, brain capillaries isolated from human brain tissue represent a unique tool to study barrier function as close to the human in vivo situation as possible. Here, we describe an optimized protocol to isolate capillaries from human brain tissue at a high yield and with consistent …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Pathogenicity And Protection Mediated By A Single Tcrβ In Experimental Autoimmune Encephalomyelitis, Tianhua Wu

Theses and Dissertations (ETD)

How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by …

A Neurotheological Approach To Spiritual Awakening, Andrew B. Newberg, Mark R. Waldman

Marcus Institute of Integrative Health Faculty Papers

A neurotheological approach suggests an analysis of spiritual awakening experiences by combining phenomenological data with neuroscience. This paper presents a synthesis combining information on the thoughts, feelings, and experiences associated with spiritual awakening experiences and neurophysiological data, primarily from neuroimaging studies, to help assess which brain structures might be associated with these experiences. Brain structures involved with emotions correlate with emotional responses while areas of the brain associated with the sense of self appear to correlate with the key feature of these experiences in which an individual loses the sense of self and feels intimately connected with God, universal consciousness, …

Validation And Optimisation Of A Touchscreen Progressive Ratio Test Of Motivation In Male Rats, Jonathan M. Hailwood, Christopher J. Heath, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Across species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only. Objectives: Touchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms. Methods: Separate groups …

Resting-State Functional Connectivity In Youth With Gender Dysphoria, Felix L. Garcia

Dissertations, Theses, and Capstone Projects

Current developmental models of gender identity and gender dysphoria (GD) lack sex-specific profiles of brain function that differentiate between typically-developing and cross-gender identified youth, as postulated by models like the unified theory of the origins of sex differences (Arnold, 2009) and the neurobiological theory of the origins of transsexuality (Swaab & Garcia-Falgueras, 2009). Previously, investigators have used brain imaging modalities such as Resting-State functional Magnetic Resonance Imaging (R-fMRI) to demonstrate differences in resting-state functional connectivity (RSFC) between typically-developing male and female youth, and between typically-developing and GID-diagnosed youth. In the present pilot study, I used R-fMRI to investigate differences in …

Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim

Community & Environmental Health Faculty Publications

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and …

Propofol Inhibits The Voltage-Gated Sodium Channel Nachbac At Multiple Sites., Yali Wang, Elaine Yang, Marta M. Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L. Klein, Roderic G. Eckenhoff, William P. Dailey, Manuel Covarrubias, Pei Tang, Yan Xu

Department of Neuroscience Faculty Papers

Voltage-gated sodium (Na_V) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic Na_V channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects …

Propofol Inhibits Prokaryotic Voltage-Gated Na+ Channels By Promoting Activation-Coupled Inactivation, Elaine Yang, Daniele Granata, Roderic G. Eckenhoff, Vincenzo Carnevale, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na⁺ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations …

Neuroprotective Functions Of Docosahexaenoic Acid And Epidermal Fatty Acid Binding Protein, Manuel Luis Montero

Loma Linda University Electronic Theses, Dissertations & Projects

Lipotoxicity (LTx) is involved in mostly every process of neuronal injury. Using NGFDPC12 cells we show that palmitic acid (PA) induces the expression of stress response genes HIF-1α and BNIP3, increases the accumulation of reactive oxygen species, and decreases cell viability by apoptosis. Inhibition of cathepsins does not rescue neurons from PA-LTx but inhibition of necroptosis and promotion of autophagy do. DHA decreases the expression of HIF-1α and BNIP3 and rescues PA-induced cell death by inhibiting apoptosis and necroptosis. Besides DHA stimulates the mRNA expression, phosphorylation and conjugation of autophagy controlling proteins. Inhibiting autophagy during DHA treatment decreases its capacity …

Ketogenic Diet Modulates Nad+-Dependent Enzymes And Reduces Dna Damage In Hippocampus, Marwa Elamin, David N. Ruskin, Susan A. Masino, Paola Sacchetti

Faculty Scholarship

© 2018 Elamin, Ruskin, Masino and Sacchetti. The ketogenic diet’s (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 …

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …

Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma

Department of Neuroscience Faculty Papers

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle …

Integrative Signaling Of Mitochondria, Trpa1 And Trpv1 In Vagal Neurons, Katherine Stanford

USF Tampa Graduate Theses and Dissertations

Sensory nerves detect conditions in the external and internal environment and permit behavioral and physiological responses to maintain homeostasis and ensure survival. As such, sensory nerves detect a wide variety of stimuli including heat, touch, pH, and vibration. The precise nature of these responses is dependent upon the initiating stimulus and site of activation. Potentially threatening stimuli (noxious heat, cellular damage, chemical irritants) activate nociceptive sensory nerves through the gating of ion channels expressed at sensory nerve terminals, thereby evoking defensive reflexes such as cough, watering eyes and limb withdrawal as well as sensations of pain or discomfort. While these …

Properties Of Synaptic Transmission From Rods And Cones In The Outer Plexiform Layer Of The Vertebrate Retina, Xiangyi Wen

Theses & Dissertations

Photoreceptors are the first neurons in the visual system. They transduce changes in light intensity into graded changes in membrane potential that are then transformed into chemical signals by regulating the release of glutamate-filled synaptic vesicles. Rod and cone photoreceptors release glutamate continuously in darkness and release slows in light. To help track rapid changes in light intensity, photoreceptors are capable of both rapid exocytosis and rapid endocytosis of synaptic vesicles.

Endocytosis is needed for recycling synaptic vesicles but also appears to be important for removing proteins and lipids from active zones to restore release site function after prior vesicle …

A-Type Kv Channels In Dorsal Root Ganglion Neurons: Diversity, Function, And Dysfunction, Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem

Department of Neuroscience Faculty Papers

A-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including highly specialized and heterogenous dorsal root ganglion (DRG) neurons. Although all A-type Kv channels display pore-forming subunits with similar structural properties and fast inactivation, their voltage-, and time-dependent properties and modulation are significantly different. These differences ultimately determine distinct physiological roles of diverse A-type Kv channels, and how their dysfunction might contribute to neurological disorders. The importance …

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …

Cardiac Autonomic Neuropathy In Diabetes: A Predictor Of Cardiometabolic Events, Aaron I. Vinik, Carolina Casellini, Henri K. Parson, Sheri R. Colberg, Marie-Laure Nevoret

Human Movement Sciences Faculty Publications

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

An Interface Of The Taste And Reward Systems In The Brainstem And Its Role In Feeding, Louis Saites

Theses and Dissertations (ETD)

We eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described.

In one sense, this neurobiology begins …