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Reduced Pain And Inflammation In Juvenile And Adult Rats Fed A Ketogenic Diet, David N. Ruskin, Masahito Kawamura Jr., Susan A. Masino

Faculty Scholarship

The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain …

Gamma Motor Neurons Express Distinct Genetic Markers At Birth And Require Muscle Spindle-Derived Gdnf For Postnatal Survival, Neil A. Shneider, Meghan N. Brown, Courtney A. Smith, James Pickel, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Gamma motor neurons (γ-MNs) selectively innervate muscle spindle intrafusal fibers and regulate their sensitivity to stretch. They constitute a distinct subpopulation that differs in morphology, physiology and connectivity from α-MNs, which innervate extrafusal muscle fibers and exert force. The mechanisms that control the differentiation of functionally distinct fusimotor neurons are unknown. Progress on this question has been limited by the absence of molecular markers to specifically distinguish and manipulate γ-MNs. Recently, it was reported that early embryonic γ-MN precursors are dependent on GDNF. Using this knowledge we characterized genetic strategies to label developing γ-MNs based on GDNF receptor expression, …

Regulation Of Energy Stores And Feeding By Neuronal And Peripheral Creb Activity In Drosophila., Koichi Iijima, Lijuan Zhao, Christopher Shenton, Kanae Iijima-Ando

Department of Biochemistry and Molecular Biology Faculty Papers

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores …

Timing Of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression Of Sensory Processing Behavior In Rhesus Monkeys, Mary L. Schneider, Colleen F. Moore, Julie A. Larson, Christina S. Barr, Onofre T. Dejesus, Andrew D. Roberts

Physics and Astronomy Department Publications

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. …

Differential Actions Of Ethanol And Trichloroethanol At Sites In The M3 And M4 Domains Of The Nmda Receptor Glun2a (Nr2a) Subunit, Ak Salous, H Ren, Ka Lamb, Xiang-Qun Hu, Rh Lipsky, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

Background and purpose:  Alcohol produces its behavioural effects in part due to inhibition of N-methyl-d-aspartate (NMDA) receptors in the CNS. Previous studies have identified amino acid residues in membrane-associated domains 3 (M3) and 4 (M4) of the NMDA receptor that influence ethanol sensitivity. In addition, in other alcohol-sensitive ion channels, sedative-hypnotic agents have in some cases been shown to act at sites distinct from the sites of ethanol action. In this study, we compared the influence of mutations at these sites on sensitivity to ethanol and trichloroethanol, a sedative-hypnotic agent that is a structural analogue of ethanol.

Experimental approach: …

Adapting To Dynamic Stimulus-Response Values: Differential Contributions Of Inferior Frontal, Dorsomedial, And Dorsolateral Regions Of Prefrontal Cortex To Decision Making., Derek G V Mitchell, Qian Luo, Shelley B Avny, Tomasz Kasprzycki, Karanvir Gupta, Gang Chen, Elizabeth C Finger, R James R Blair

Brain and Mind Institute Researchers' Publications

Dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), and inferior frontal gyrus (IFG) have all been implicated in resolving decision conflict whether this conflict is generated by having to select between responses of similar value or by making selections following a reversal in reinforcement contingencies. However, work distinguishing their individual functional contributions remains preliminary. We used functional magnetic resonance imaging to delineate the functional role of these systems with regard to both forms of decision conflict. Within dmPFC and dlPFC, blood oxygen level-dependent responses increased in response to decision conflict regardless of whether the conflict occurred in the context of …

Safe Emergency Management Of Acute Ischemic Stroke: An Academic Community Hospital Decade Experience, John Castaldo, Richard S. Mackenzie Md, Peter J. Barbour Md, Lorraine Spikol, Yevgeniy Isayev, Yuebing Li Phd, Gary Clauser Md, John Margraf Md, Glenn Mackin Md, Faan, Facp, David Richardson, Gavin C. Barr, Jr. Md, Donna Jenny, Susan Nevada, Claranne Mathiesen

Department of Emergency Medicine

No abstract provided.

Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

The prevailing view of the medial temporal lobe (MTL) holds that its structures are dedicated to long-term declarative memory. Recent evidence challenges this position, suggesting that perirhinal cortex (PRc) in the MTL may also play a role in perceptual discriminations of stimuli with substantial visual feature overlap. Relevant neuropsychological findings in humans have been inconclusive, likely because studies have relied on patients with large and variable MTL lesions. Here, we conducted a functional magnetic resonance imaging study in healthy individuals to determine whether PRc shows a performance-related involvement in perceptual oddball judgments that is comparable to its established role in …

Defining Family: Naming, Orientation, And Redemption In The Case Of Terri Schiavo, M. Chad Mcbride, Karen L. Taas, Paige W. Toller

Communication Faculty Publications

This paper undertakes a detailed analysis of the Terri Schiavo case as it was covered in popular media. Drawing on Burkean theory, we argue a critical issue in the case was a struggle between Terri's parents and husband to be seen as the more legitimate family in order to determine the duration and extent of Terri 's medical care. We discuss how the private debate over Terri's health and the decision to remove her feeding tube entered into the public scenes of legal and political action. This shift to the public scene represented problems for the parties directly involved in …

Neuroadaptations In The Cellular And Postsynaptic Group 1 Metabotropic Glutamate Receptor Mglur5 And Homer Proteins Following Extinction Of Cocaine Self-Administration, M. Behnam Ghasemzadeh, Preethi Vasudevan, Christopher Mueller, Chad Seubert, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

This study examined the role of group1 metabotropic glutamate receptor mGluR5 and associated postsynaptic scaffolding protein Homer1b/c in behavioral plasticity after three withdrawal treatments from cocaine self-administration. Rats self-administered cocaine or saline for 14 days followed by a withdrawal period during which rats underwent extinction training, remained in their home cages, or were placed in the self-administration chambers in the absence of extinction. Subsequently, the tissue level and distribution of proteins in the synaptosomal fraction associated with the postsynaptic density were examined. Cocaine self-administration followed by home cage exposure reduced the mGluR5 protein in nucleus accumbens (NA) shell and dorsolateral …

To See Or Not To See: Prestimulus Α Phase Predicts Visual Awareness, Kyle E. Mathewson, Gabriele Gratton, Monica Fabiani, Diane M. Beck, Tony Ro

Publications and Research

We often fail to see something that at other times is readily detectable. Because the visual stimulus itself is unchanged, this variability in conscious awareness is likely related to changes in the brain. Here we show that the phase of EEG α rhythm measured over posterior brain regions can reliably predict both subsequent visual detection and stimulus-elicited cortical activation levels in a metacontrast masking paradigm. When a visual target presentation coincides with the trough of an α wave, cortical activation is suppressed as early as 100 ms after stimulus onset, and observers are less likely to detect the target. Thus, …

Mathematics Deficiencies In Children With Very Low Birth Weight Or Very Preterm Birth, H. Gerry Taylor, Kimberly A. Espy, Peter J. Anderson

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Abstract Children with very low birth weight (VLBW, < 1500 g) or very pre-term birth (VPTB, < 32 weeks gestational age or GA) have more mathematics disabilities or deficiencies (MD) and higher rates of mathematics learning disabilities (MLD) than normal birth weight term-born children (NBW, > 2500 g and > 36 weeks GA). MD are found even in children without global disorders in cognition or neurosensory status and when IQ is controlled, and they are associated with other learning problems and weaknesses in perceptual motor abilities and executive function. Factors related to poorer mathematics outcomes include lower birth weight and GA, neonatal complications, and possible abnormalities in brain structure. While little is known about the nature of MD in these children, studies of MLD in other neurodevelopmental disorders and in children with learning disabilities provide useful models for further …

Age-Related Differences In Reaction Time Task Performance In Young Children, Sergey Kiselev, Kimberly A. Espy, Tiffany Sheffield

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Performance of reaction time (RT) tasks was investigated in young children and adults to test the hypothesis that age-related differences in processing speed supersede a “global” mechanism and are a function of specific differences in task demands and processing requirements. The sample consisted of 54 4-year-olds, 53 5-year-olds, 59 6-year-olds, and 35 adults from Russia. Using the regression approach pioneered by Brinley and the transformation method proposed by Madden and colleagues and Ridderinkhoff and van der Molen, age-related differences in processing speed differed among RT tasks with varying demands. In particular, RTs differed between children and adults on tasks that …

Naloxone's Pentapeptide Binding Site On Filamin A Blocks Mu Opioid Receptor–Gs Coupling And Creb Activation Of Acute Morphine, Hoau-Yan Wang, Lindsay H. Burns

Publications and Research

Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Gαs and its Gβγ dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 µM …

Viewing Preschool Disruptive Behavior Disorders And Attention-Deficit/Hyperactivity Disorder Through A Developmental Lens: What We Know And What We Need To Know, Anil Chacko, Lauren Wakschlag, Carri Hill, Barbara Danis, Kimberly A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Although DSM-defined DBDs and ADHD manifest during early childhood in meaning¬ful ways, the emphasis of extending the DBD and ADHD nosology, which is based on studies of older youth, to younger children potentially limits the utility of these symptoms. Given that it is clear that DBDs and ADHD often emerge during early childhood and that early intervention is most efficacious, developing a more refined understanding of the clinical phenomenology of behavior disorders in early childhood is a critical next step. We contend that an approach that emphasizes the developmental specification of symptoms has the potential to address several long-standing issues …

Growth Mixture Modeling Of Academic Achievement In Children Of Varying Birth Weight Risk, Kimberly A. Espy, Julia Hua Fang, David Charak, Nori Minich, H. Gerry Taylor

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The extremes of birth weight and preterm birth are known to result in a host of adverse outcomes, yet studies to date largely have used cross-sectional designs and variable-centered methods to understand long-term sequelae. Growth mixture modeling (GMM) that utilizes an integrated person- and variable-centered approach was applied to identify latent classes of achievement from a cohort of school-age children born at varying birth weights. GMM analyses revealed 2 latent achievement classes for calculation, problem-solving, and decoding abilities. The classes differed substantively and persistently in proficiency and in growth trajectories. Birth weight was a robust predictor of class membership for …

Power Of Models In Longitudinal Study: Findings From A Full- Crossed Simulation Design, Hua Fang, Gordon P. Brooks, Maria L. Rizzo, Kimberly A. Espy, Robert S. Barcikowski

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Because the power properties of traditional repeated measures and hierarchical multivariate linear models have not been clearly determined in the balanced design for longitudinal studies in the literature, the authors present a power comparison study of traditional repeated measures and hierarchical multivariate linear models under 3 variance-covariance structures. The results from a full-crossed simulation design suggest that traditional repeated measures have significantly higher power than do hierarchical multivariate linear models for main effects, but they have significantly lower power for interaction effects in most situations. Significant power differences are also exhibited when power is compared across different covariance structures.

Proximal Sciatic Nerve Intraneural Ganglion Cyst, Karin R. Swartz, Dianne Wilson, Michael Boland, Dominic B. Fee

Neurosurgery Faculty Publications

Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009.

Mitochondrial Fragmentation Is Involved In Methamphetamine-Induced Cell Death In Rat Hippocampal Neural Progenitor Cells., Changhai Tian, L. Charles Murrin, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen …

Persistencia De Anticuerpos Maternales Contra El Virus De La Peste Porcina Clásica En Lechones Nacidos De Marranas En Granjas Con Diferentes Estrategias De Vacunación, Katherine J. Portilla, Albert Manchego S., Hermelinda G. Rivera, Mariluz Araínga, Marcy Ramierz V.

Journal Articles: Pharmacology & Experimental Neuroscience

In the study evaluated was the persistence of maternal antibodies levels Classical Swine Fever Against the virus (CSFV) in Vaccinated piglets born from sows from two farms (A and B) With different strategies against CSFV vaccination. In farm A sows were vaccinated at 90 days of gestation and in farm B at 18 - 21 days postpartum. Serum samples were collected from piglets of both farms, at first (n=15), third (n=15), fifth (n=15) and seventh (n=15) weeks of age, and from 15 sows from each farm A for detection of antibodies against CSFV by the indirect ELISA test. All piglets …

Aerobic Fitness And Cognitive Development: Event-Related Brain Potential And Task Performance Indices Of Executive Control In Preadolescent Children, Jason Themanson, Charles Hillman, Sarah Buck, Matthew Pontifex, Darla Castelli

Scholarship

The relationship between aerobic fitness and executive control was assessed in 38 higher- and lower-fit children (Mage = 9.4 years), grouped according to their performance on a field test of aerobic capacity. Participants performed a flanker task requiring variable amounts of executive control while event-related brain potential responses and task performance were assessed. Results indicated that higher-fit children performed more accurately across conditions of the flanker task and following commission errors when compared to lower-fit children, whereas no group differences were observed for reaction time. Neuroelectric data indicated that P3 amplitude was larger for higher- compared to lower-fit children across …

Pattern Recognition Of Longitudinal Trial Data With Nonignorable Missingness: An Empirical Case Study, Julia Hua Fang, Kimberly A. Espy, Maria L. Rizzo, Christian Stopp, Sandra A. Wiebe, Walter W. Stroup

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Methods for identifying meaningful growth patterns of longitudinal trial data with both nonignorable intermittent and drop-out missingness are rare. In this study, a combined approach with statistical and data mining techniques is utilized to address the nonignorable missing data issue in growth pattern recognition. First, a parallel mixture model is proposed to model the nonignorable missing information from a real-world patient-oriented study and concurrently to estimate the growth trajectories of participants. Then, based on individual growth parameter estimates and their auxiliary feature attributes, a fuzzy clustering method is incorporated to identify the growth patterns. This case study demonstrates that the …

The Efficacy Of Surgical Decompression Before 24 Hours Versus 24 To 72 Hours In Patients With Spinal Cord Injury From T1 To L1--With Specific Consideration On Ethics: A Randomized Controlled Trial., Vafa Rahimi-Movaghar, Soheil Saadat, Alexander R Vaccaro, Seyed Mohammad Ghodsi, Mohammad Samadian, Arya Sheykhmozaffari, Seyed Mohammad Safdari, Bahram Keshmirian

Department of Neurosurgery Faculty Papers

BACKGROUND: There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24-72 hours) surgical decompression in terms of neurological …

Complementary Responses To Mean And Variance Modulations In The Perfect Integrate-And-Fire Model, Joanna R. Wares, Todd W. Troyer

Department of Math & Statistics Faculty Publications

In the perfect integrate-and-fire model (PIF), the membrane voltage is proportional to the integral of the input current since the time of the previous spike. It has been shown that the firing rate within a noise free ensemble of PIF neurons responds instantaneously to dynamic changes in the input current, whereas in the presence of white noise, model neurons preferentially pass low frequency modulations of the mean current. Here, we prove that when the input variance is perturbed while holding the mean current constant, the PIF responds preferentially to high frequency modulations. Moreover, the linear filters for mean and variance …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …