Schedule for Neuroscience Day
February 2, 2007
8:00-9:00Registration and Poster setup
9:30-9:40Welcome
9:40-9:55Dr. Mark Greenwald
9:55-10:05Dr. Don Cocina
10:05-10:15 Dr. Graham Parker
10:15-10:25Dr. Ava Senkfor
10:25-10:35Dr. Scott Bowen
10:40-11:00Break with refreshments, poster preview
11:00-11:20Chaim Cohlen, student talk
11:20-11:40Joseph McClure, student talk
11:40-12:00Shonagh O’Leary-Moore, student talk
12:00-3:00lunch and poster viewing
3:00-3:15Dr. John Kamholz
3:15-3:25Dr. Jeffrey Loeb
3:25-3:35Dr. Larry Grossman
3:35-3:45Dr. Douglas Ruden
3:45-3:55Dr. Dr. Nitin Chouthai
4:00-5:00Keynote speaker – Tom Carew
How Time Flies: The Molecular Architecture of Memory
5:15poster cleanup
All events will be held in McGregorConferenceCenter on the Campus of Wayne State University. Posters and refreshments will be in the lobby. All talks will be in room BC. Lunch will be downstairs in room M.
Table of Contents
Page 1 ……………………………Schedule
Page 2 ……………………………Dr. Tom Carew
Page 3 ……………………………Faculty Talk Titles
Page 4 ……………………………Student Talk Abstracts
Page 6 ……………………………Poster Abstracts
Page 15 ……………………………Attendees/Presenter Index
Page 18 ……………………………WSU Graduate Student Neuroscience Society
Page 19 ……………………………WSU Neuroscience Information
Page 20 ……………………………Neuroscience Colloquium 2006-07 Schedule
We thank the Office of the Vice President for Research, the College of Liberal Arts and Sciences, and the Departments of Biological Sciences and Psychology for sponsoring this event and the Neuroscience Colloquium.
Cover Credits: Drosophila showing the nerve cord - VanBerkum Lab (bottom center); Retinal Ganglion Cell - Myhr Lab (bottom right); and clip art
Faculty Talk Titles
Faculty Talks (in order of appearance)
Morning Session
Dr. Mark Greenwald, Department of Psychiatry and Behavioral Neurosciences, School of Medicine -“Neuropsychophamacology of Drug Abuse”
Dr. Don Cocina, Department of Psychology, College of Liberal Arts and Sciences - “Urocortins, Obesity and Whole-Body Metabolism”
Dr. Graham Parker, Department of Pediatrics, School of Medicine – title TBA
Dr. Ava Senkfor, Department of Psychology, College of Liberal Arts and Sciences - “Neural Investigations of Memory and Multisensory Experience”
Dr. Scott Bowen, Department of Psychology, College of Liberal Arts and Sciences - “Developmental Toxicity of Prenatal Exposure to Toluene”
Afternoon Session
Dr. John Kamholz, Department of Neurology, School of Medicine and Center for Molecular Medicine and Genetics -“Molecular Pathophysiology of Demyelinating Disease”
Dr. Jeffrey Loeb, Department of Neurology and Center for Molecular Medicine and Genetics - “When learning too much goes wrong: Molecular pathways, synapses
and cells in human epilepsy”
Dr. Larry Grossman, Center for Molecular Medicine and Genetics - “Function and Evolution of Mitochondria”
Dr. Douglas Ruden, Institute of Environmental Health Sciences and Department of Biochemistry - “Epigenetics and Pb Toxicogenomicsin Drosophila”
Dr. Nitin Chouthai, Department of Pediatrics and Children’s Research Center of Michigan - “Cellular Events during Human Neurodevelopment and Neurotrophic Factors”
Keynote Seminar
Dr. Tom Carew, Bren Professor and Chair of the Department of Neurobiology and Behavior, University of California, Irvine - “How Time Flies: The Molecular Architecture of Memory”
Student Talks
Chaim Colen, Murali Guthikonda, Andrew Sloan, and Saroj Mathupala
Department of Physiology, School of Medicine
Radiosensitization By Inhibiting The Monocarboxylate Transport In Malignant Glioma: An In-Vivo Study
Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor, and patient survival remains dismal with conventional therapies. Targeting its lactate transporter in vitro results in selective glioma cytotoxic death that can be enhanced with low-dose irradiation. For the first time, we applied this technique in human intracranial gliomas implanted in a nude rat model. We hypothesized inhibition of lactate/pyruvate transport would induce tumor apoptosis by reducing antioxidant protection, and, thus, deplete the tumor cell's defense against free radicals. Irradiating these antioxidant depleted cells would make them highly vulnerable to free radical provoked damage. Thirty-two 3 week old nude rats (NU) were divided into 2 main groups; those receiving tumor and those without. Subgroups were; no treatment, drug alone, irradiation alone, drug and irradiation, or irradiation and anti-Monocarboxylate-siRNA therapy. Twenty-eight rats underwent stereotactic implantation of U87-MG glioma cells into their frontal lobe. Tumors were allowed to grow for 2 weeks. Then, osmotic pumps were implanted to deliver drug (alpha-cyano-4-hydroxycinnamic acid (ACCA)) or adenovirus therapy (MCT-specific small-interfering RNA (siRNA)). Stereotactic gamma irradiation (Leksell) was delivered using our specially engineered MRI-compatible rat head-holder. Tumor growth/shrinkage was volume-quantified by small animal MRI and then quantitated by histology. Survival fractions were determined and plotted using Kaplan-Meier survival curves. We found that both drug and MCT-specific gene therapy mediated 1) reduced tumor volume (glioma selective cytotoxicity), 2) sensitized the cells to irradiation damage and 3) improved survival with minimal side effects. We concluded that the localized use of a lactate transport inhibitor in-vivo is non-toxic and is a novel adjunctive therapeutic strategy against glial tumors, which can be combined with radiotherapy for increased efficacy. An upcoming Phase I study should reveal tolerance and feasibility of this therapeutic strategy in the treatment of human tumors.
Joseph McClure, and Taduesz Scislo
Department of Physiology, School of Medicine
Mechanisms Mediating Regional Vascular Responses to Stimulation of Adenosine A1 Receptors in the Nucleus of the Solitary Tract (NTS)
Our previous study showed that stimulation of NTS adenosine A1 receptors exerts variable, counteracting effects on the iliac vascular bed: activation of the adrenal medulla and -adrenergic vasodilation vs. vasoconstriction mediated by neural and unknown humoral factors (McClure et al. Am J Physiol Heart Circ Physiol 289, 2005). Stimulation of NTS A1 receptors increases sympathetic nerve activity releasing norepinephrine and may attenuate the baroreflex, thus increasing circulating vasopressin. Therefore we investigated the role of vasopressin and sympathetic nerves in NTS A1 receptor mediated iliac vasoconstriction. We compared the integral responses (∫%) of mean arterial pressure (MAP) and iliac conductance (IVC) in 5 groups of chloralose/urethane anesthetized rats: intact (INT), following vasopressin V1 receptor blockade (VX), VX and lumbar sympathectomy (VX+LX), ganglionic blockade and adrenalectomy (GX+ADX) and combined GX+ADX+VX. In INT, typical variable responses were observed (MAP=93.0±90.9, IVC=-127.1±101.6). VX reversed the responses to depressor (-136.2±60.5) and vasodilatory ones (95.5±85.0). VX+LX accentuated the depressor (-279.9±50.2) and vasodilatory responses (426.9±110.4). GX+ADX accentuated the pressor (353.6±69.1) and vasoconstrictor (-624.9±103.3) responses. GX+ADX+VX abolished this accentuation (MAP=64.9±37.0, IVC-200.8±35.6). We conclude that the release of vasopressin triggered by stimulation of NTS A1 receptors is a major vasoconstrictor factor opposing -adrenergic vasodilation in the iliac vasculature. In the follow-up studies we compared the responses of iliac vs. mesenteric and renal vascular conductance (IVC, MVC and RVC, respectively) in 4 groups of rats: INT, X, ADX, VX. In INT, typical biphasic responses were observed: early vasodilation (tended: IVC=RVC>MVC) followed by vasoconstriction. Both ADX and X abolished the vasodilation (to a greater extent in βX). VX abolished/reversed iliac and mesenteric but not renal vasoconstrictor responses. We conclude that -adrenergic and vasopressinergic mechanisms differentially contribute to regional vascular responses evoked by stimulation of NTS adenosine A1 receptors. Supported by NIH HL-67814.
Shonagh O’Leary-Moore, Andrew McMechan, Matthew Galloway, John Hannigan
Departments of Psychology, OB/GYN, and Psychiatry, College of Liberal Arts and Sciences and the School of Medicine
DEVELOPMENT-DEPENDENT CHANGES IN CEREBELLAR NEUROCHEMISTRY AFTER NEONATAL ALCOHOL EXPOSURE MEASURED BY MAGNETIC RESONANCE SPECTROSCOPY
Non-invasive magnetic resonance imaging techniques may aid in identifying biomarkers of fetal alcohol effects. Because the cerebellum is particularly vulnerable to the teratogenic effects of alcohol exposure, we used a rat model of third-trimester alcohol exposure and high-resolution magic angle spinning MRS (HR-MAS 1H MRS) to assess neurochemistry after neonatal alcohol exposure. Male and female rat pups were given 5 g/kg alcohol via gastric intubation from postnatal (PN) days 4-9. Controls were sham- or non-intubated. At PN16, PN28, or PN63, brains were harvested and ~5-mg punches taken from cerebellar vermis. For HR-MAS, samples were spun in a zirconium rotor using a Bruker 11.7-Tesla spectrometer at a rate of 4.2kHz @ 54º7' relative to B0. A chemical shift spectrum of MR-visible neurochemicals, including N-acetyl-aspartate (NAA), glutamate, GABA, glutamine, creatine, choline, glutathione, taurine, and myo-inositol was acquired for each sample using a CPMG rotor-synchronized pulse sequence and quantified using LC Model. Results indicated that at PN16, levels of NAA, taurine, and glutatmate were significantly reduced in alcohol-exposed rats compared to both sham- and non-intubated controls. At PN28, these reductions persisted but alcohol-exposed animals only differed significantly compared to non-intubated controls. By PN63, there were no significant differences in any neurochemical after neonatal alcohol exposure. Reduced NAA may be reflective of compromised neuronal viability in the cerebellum following neonatal alcohol exposure. Results may also be indicative of a developmental delay followed by recovery associated with neonatal alcohol exposure because no differences were apparent at PN63. The use of HR-MAS 1H-MRS to examine changes in neurochemistry provides novel insight into the mechanism(s) of developmental brain damage following fetal alcohol exposure. Supported in part by F31 -AA15224-01 (SOLM), R01-AA12015 (JHH), R01-DA16736 (MPG), and the Brain Imaging Research Division of the WSU School of Medicine.