NRCnewsletter

http://nba.uth.tmc.edu/nrc/ News & Featured Research of the Neuroscience Research Center volume 14, number 01, Winter 2008

Multiple sclerosis (MS) is the most common inflammatory and demyelinating disease of man. It is the leading cause of non-traumatic chronic neurologic disability of young adults. While the early clinical course of the disease is usually relapsing and remitting, most untreated patients eventually accumulate disability in episodic fashion and eventually enter into a phase of the disease characterized by unrelenting deterioration.

Lesions can occur anywhere throughout the central nervous system where myelin is expressed. Newly formed lesions show evidence of active perivascular inflammation, parenchymal infiltration by T lymphocytes and macrophages, active degradation of myelin and variable amounts of axonal transaction. Chronic lesions show little or no evidence of ongoing inflammation, loss of myelin and axons, and variable amounts of astrogliosis. The root cause of the disease is unknown and the relative importance of the balanced interplay of complex genetics, environmental and hormonal influences on disease expression and course remain poorly understood.

Nonetheless, with the advent of the application of modern clinical trial design to the insights gained from models of organ-specific autoimmune diseases such as experimental allergic encephalomyelitis, multiple sclerosis clinical trialists have substantial advanced our ability to at least partially control the disease through increasingly targeted manipulation of the immune system. Relatively simple immunomodulatory drugs with pleiotrophic effects like the beta interferons and glatiramer acetate convincingly reduce the number of clinical episodes, and retard magnetic resonance imaging (MRI)-defined and clinically measured disease progression. More recently, monoclonal

The concept of ‘chemical synapse’ outlined in most neuroscience textbooks is that of a specialized junction between a presynaptic ending formed by an axon, which releases neurotransmitter in response to presynaptic activity and a postsynaptic structure that expresses the appropriate set of ionotropic or metabotropic receptors. This view of synaptic transmission as the rapid signal transfer between two excitable cells has

undergone significant revision in recent years and now includes a third player, astrocytes. Astrocytes and oligodendrocytes constitute the two major subtypes of glia in the CNS. Whereas mature oligodendrocytes form the myelin which ensheaths CNS axons, astrocytes are intimately associated with chemical synapses. Like their neuronal cousins, they express a variety of receptors for neurotransmitters, allowing them to respond to activity at nearby synapses with increases in cytosolic Ca2+ levels or G protein activation. That in turn can trigger the release of a ‘gliotransmitter’, which can modulate transmitter release at nearby synapses, activate postsynaptic receptors, or regulate local blood flow via vasodilation. Astrocytes are therefore active participants in brain function and can potentially modulate synaptic transmission on rapid time scales.

Neuron-glia signalingAstrocytes were long considered silent, if critical, bystanders

of fast synaptic transmission. Among the key roles carried out by astrocytes are metabolic support and the uptake of neurotransmitters. Early hints that astrocytes might play a more active role during fast synaptic transmission came from observations that they respond to the application of neurotransmitters with elevations in their internal Ca2+ levels. More importantly, various synaptically released chemicals were then discovered that were able to elevate astrocytic Ca2+ levels, including glutamate, noradrenaline, histamine, acetylcholine, ATP, GABA and nitric oxide.

Most astrocytes are not directly targeted by ultrastructurally defined synaptic contacts. Thus, transmitter released from synapses has to spill out of the synaptic cleft to activate extrasynaptic receptors expressed in nearby astrocytes. Whether

The next generation of therapeutic agents for multiple sclerosis

By Jerry S. Wolinsky, M.D.

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Gliotransmission in the Central Nervous System

By Michael Beierlein, Ph.D.

Wolinsky

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Ground breaking at Houston’s Research Park Complex and opening of the new Medical School Research SpaceFrom the director, John H. Byrne, Ph.D.

The University of Texas in Houston continues to grow. After a ground breaking ceremony at the end of August, 2007, construction was begun on the University of Texas Health Science Center

at Houston’s Research Park Complex. This complex will encompass 393,000 gross square feet, will cost $161.5 million, and will house three independent programs which are presently housed in separate buildings. This complex will consist of the Dental Branch Replacement Building, the Biomedical Research and Education facility (focusing on stem cell research), and the Neuroscience Building. This research complex will cover 7.5 acres of the 45 acres of the UT Research Park which is under development jointly by UTHSC-Houston and the UT MD Anderson Cancer Center.

The Neuroscience Center, a $22.9 million facility, is expected to be completed by the Fall of 2009. It will have a total of 69,000 square feet of space, and will house the Department of Psychiatry and Behavioral Sciences faculty and staff as well as research and clinical space. Collaborative research should include more than 250 research scientists, and the combination of basic research and clinical trials will dovetail nicely with the goals of the recently established Center for Clinical and Translational Sciences, supported by the NIH. Expanding the field of neuroscience research into human behavior and the causes of debilitating conditions, such as addiction or compulsive behavior, is an exciting and growing field of study.

Closer to home, the Medical School’s new Research Space will be open in early 2008, although a ribbon cutting ceremony officially opened the facility on December 14, 2007 in conjunction with tours of the new facility. It was built on the site of the two-story John Freeman Building, and

Byrne

provides 200,673 additional gross square feet for offices and laboratories for about 30 research faculty at a cost of $80.5 million. It is connected to the Medical School on several floors to promote collaboration and communication, and worldwide faculty searches are underway to fill new positions with faculty in several fields, including neurobiology. Already in place is the NRC’s Dr. Michael Beierlein, a recent recruit from Harvard Medical School who studies mechanisms of synaptic plasticity in neocortical networks. He will be joined in the spring by Dr. Wei Chen from Yale who studies how odor information is coded, processed and stored in mammalian olfactory bulb. Both are new faculty in the Department of Neurobiology and Anatomy. The Department of Pediatrics has already hired Dr. Michael Gambello, whose research covers the diagnosis and management of genetic and metabolic disorders, including tuberous sclerosis complex and autism, and Dr. Seonhee Kim, whose research interests include molecular and cellular mechanisms of development in the cerebral cortex.

Of particular importance to many

of us, the upper floors of the Research Space is a new state-of-the-art vivarium. Portions of the new nonhuman primate facility and mouse facility were built with major grants from the NIH and represent the best laboratory conditions available for research animals. The old vivarium had been in the Medical School’s basement, which was flooded and destroyed during Tropical Storm Allison in June 2001, taking the lives of hundreds of research animals. The new facility has a ground floor elevation above the 500 year flood plain, and the animals are housed on the building’s upper floors. For the first time in six and a half years, all animal care facilities and resources will be centralized in an area where the dedicated vivarial staff can once again work as a unit.

The Texas Medical Center continues to grow, and UTHSC-Houston and the Medical School are growing with it. With current construction plans, it is estimated that by 2014 the Texas Medical Center will have 40 million square feet dedicated to patients, research and education, and the work force will have increased from the present 70,000 to 100,000.

Medical School Research Space opened in December 2007.

Since 1991, the Fall Meeting of the Association

of Neuroscience Departments and Programs

has included the presentation of the Award for

Education in Neuroscience to an individual in

recognition of their outstanding contributions

to research, education and a distinguished

career in the neurosciences. The 2007

recipient of the ANDP Award for Education in

Neuroscience was John H. Byrne, Ph.D., Director

of the Neuroscience Research Center.

Pedro Ruiz, M.D., professor and interim chair

of the Department of Psychiatry and Behavioral

Sciences, was appointed as a member of the

following Editorial Boards: International Review

of Psychiatry (England), International Journal

of Social Psychiatry (England), Cross-Cultural

Mental Health (England) and Romanian

Journal of Psychopharmacology (Romania).

Sean Savitz, M.D., assistant professor of

neurology, is among the new Howard Hughes

Medical Institute (HHMI) Early Career Award

recipients. Each year, alumni of the HHMI-

National Institutes of Health Research Scholars

Program and the HHMI Research Training

Fellowships for Medical Students are invited to

apply for Early Career Awards as they begin their

careers as physician-scientists. Each awardee

will receive funding over a five-year period.

Savitz is focusing his research on the chemical

necrostatin, which inhibits cell death, such as

occurs in the brain during a stroke. Savitz is

working to develop necrostatin as a therapy

for stroke and in combination with the only

currently approved agent for stroke, tissue

plasminogen activator. His goal is to develop a

therapy that will protect patients from brain cell

death after they suffer a stroke.

Members of the Department of Neurology,

Mya C. Schiess, M.D., professor and the

Adriana Blood Chair in Neurology, Gage Van Horn, M.D., professor and vice chair, and Erin Furr-Stimming, M.D., assistant professor, were

presented with the Roy H. Cullen, Quality of

Life Award at the Polo for Parkinson’s fundraiser

on Sept. 30. The three serve on the medical

advisory committee of the Houston Area

Parkinson’s Society, a nonprofit organization

that meets the needs of patients with

Parkinson’s by educating and assisting patients

with emergency financial aid and social work.

Nine NRC members were named as “America’s

Top Doctors” by Castle Connolly Medical Ltd.

For 2007. These included James T. Willerson M.D., James A. Ferrendelli, M.D., Ernesto Infante, M.D., James C. Grotta, M.D., Jerry S. Wolinsky M.D., Maureen Mayes, M.D., Hope Northrup, M.D., William H. Donovan, M.D. and

Gerard Francisco M.D.

Honors

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Michael S. Beauchamp, National Science Foundation, Collaborative Research: Multisensory Influences on Touch Perception: FMRI, MEG and TMS Studies

Pramod Dash, NIH, Tuberous Sclerosis Complex in Memory Formation.

William H. Donovan, Innovative Knowledge Dissemination and Utilization for Disability and Professional Organizations and Stakeholders and the Sub-award Agreement between Boston University and TIRR; TIRR, Texas Model Spinal Cord Injury System.

Valentin Dragoi, James S. McDonnell

Foundation, , State-Dependent Cortical Activity and Visual Behavior.

Carin A. Hagberg, Foundation for Anesthesia Education and Research, Anticipation of the Difficult Airway: Preoperative Airway Assessment Form.

Vasanthi Jayaraman, NIH, Conformational Changes in Glutamate Receptor.

Steve Massey, NIH, Neurotransmitter Mechanisms in the Mammalian Retina.

Ferid Murad, NIH, The Role of Nitric Oxide and Cyclic GMP in Stem Cells.

Sean I. Savitz, American Heart Association, Texas, Defining Mammalian Pathways of Neuronal Necrosis.

Alex Valadka, Baylor College of Medicine, Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain.

Jerry S. Wolinsky, Sanofi-Aventis U.S., Study LTS 6050: Long-Term Extension to EFC6049 (Aventis 3001).

Xiurong Zhao, NIH, PPARG in Macrophage Promote Hematoma Absorption after Intracerebral Hemorrhage.

NRCUpcoming Events

The 13th Annual Public Forum for

Brain Awareness Week

Stems Cells—Their Potential for Neurological Disease

Saturday, March 1, 2008 UTHSC-Houston

Medical School Building 6431 Fannin St.,

Third Floor, Room 3.001 10:30 AM to 12:00 noon

Brain Awareness Week

March 10–16, 2008

Partners In Education

Brain Night for Children

Thursday, March 20, 2008 The Health Museum, 1515 Hermann Drive

6:00 to 8:00 PM

Awards

Volume 14, numBer 01 | Winter 20084

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this can occur under physiological conditions not only depends on receptor affinity and on their distance from sites of exocytosis but also on the density of transmitter transporters lining the extracellular space. In contrast to astrocytes, a heterogeneous group of glial precursor cells termed oligodendrocyte precursor cells is targeted directly by synaptic contacts or exocytotic release sites in axons, demonstrating that fast synaptic signaling is not exclusive to neurons.

Mechanisms of transmitter release from astrocytesAstrocytes do not express voltage-gated Ca2+ conductances at

high enough densities, so how are glial Ca2+ transients generated? The basic steps that lead to intracellular Ca2+ signals typically involve the activation of G-protein-coupled receptors and phospholipase C, and the production of IP3, which then triggers Ca2+ release from the endoplasmic reticulum. The resulting increases in Ca2+ can be highly localized and transient. However, in some systems such as the retina, activation of glia evokes Ca2+ increases that propagate as waves through neighboring glia at distances of up to several hundred micrometers.

Glial Ca2+ increases evoked by neuronal activity could be regarded as a curious epiphenomenon of limited functional importance if it were not for the fact that they initiate additional responses. Most notably, they can trigger neurotransmitter release from astrocytes. Several transmitters have been identified, including glutamate, ATP, D-serine and taurine, and others are likely to follow in the near future.

What mechanisms underlie release? Increasing evidence suggests that transmitter release from astrocytes shares common features with release from synapses. Gliotransmission is calcium-dependent as exogenous Ca2+ buffers such as BAPTA can block release whereas photolysis of caged Ca2+ can trigger it. Furthermore, neurotoxins that block exocytosis have been shown to block release from astrocytes. More recently, so-called synaptic-like vesicle compartments have been found in astrocytes that can express a number of proteins governing exocytosis as well as the vesicular glutamate transporter VGLUT, a protein crucial for the accumulation of glutamate in vesicles.

A number of questions concerning the mechanisms of transmitter release from astrocytes remain to be investigated. First, where does release occur? There is no evidence for active zones, morphologically defined sites of transmitter release, or even a distinct accumulation of vesicles near the membrane. Second, what is the calcium sensor of release? At conventional synapses, fast transmitter release is mediated by Ca2+ increases in the high micromolar range, reached in so-called microdomains. In glia, Ca2+ signals mediated by slow release from internal stores are likely to be much smaller, suggesting distinct properties for the glial Ca2+ sensor. There is also evidence for other, non-exocytotic forms of release such as volume-regulated ion channels or gap junction hemi-channels, though it remains to be seen how relevant they are under physiological conditions.

Regulation of synaptic strength by gliotransmittersOne of the most compelling preparations for fast synaptic

modulation by a gliotransmitter is the neuromuscular junction, where perisynaptic Schwann cells are responsible for half of the synaptic depression seen during repetitive stimulation of the motor nerve. Release of acetylcholine and ATP from the presynaptic terminal activates Schwann cells, evoking G-protein-dependent release of a gliotransmitter, most likely glutamate, ultimately resulting in decrease of transmitter release from the motor nerve. Interestingly, Schwann cells can also mediate

a potentiation of release via a calcium-dependent mechanism, suggesting that different mechanisms can interact to ultimately control synaptic strength.

In the hippocampus, inhibitory synapses between interneurons of the stratum radiatum and CA1 pyramidal cells can experience potentiation following interneuron activity. This potentiation is mediated by glutamate release from neighboring astrocytes, which are activated by GABA released from interneurons. The released glutamate activates AMPA and NMDA receptors on interneurons, potentiating transmitter release. At excitatory synapses, there is evidence for SNARE-dependent release of ATP from astrocytes, which is rapidly broken down to adenosine that then inhibits neurotransmission via presynaptic adenosine receptors.

Neuron-glia signaling in the cerebellumHow widespread is glial modulation of synaptic transmission

and can it occur under physiological conditions? In work I conducted in the laboratory of Wade Regehr we tested whether

Figure 1: Brief bursts of parallel fiber (PF) stimulation evoke calcium responses in Bergmann glia cells (BGs). (A) BG filled with fluorescent dye and visualized using 2-Photon microscopy. Area outlined by box indicates the region selected for calcium imaging. (B) Close-up of BG process. Dot indicates site of PF stimulation. (C) Calcium response (top) and current (bottom) recorded from BG in response to a brief stimulus train applied to PFs.

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antibodies that at first blush target highly specific cell populations and their functions have produced even more striking reductions in the frequency of clinically expressed attacks and their MRI-defined subclinical counterpart, gadolinium enhancements.

In the light of these therapeutic advances, why should multiple sclerosis specialists expect that the next generation of therapeutics is as or more likely to arise from a detailed understanding of glial cell biology and axonal glial interactions as from advances in immunology? An interesting feature of immune cells and glial cells is their partial sharing of language. Many of the soluble mediators of communication between immune cells are as likely to find their cognate ligands on glial and nerve cells as on other immune cells, depending upon the environment in which they find themselves; the reverse is also true. Lymphocytes, particularly those with a Th2 cytokine secretion profile bias that includes brain derived neurotrophic factor (BDNF) may contribute to neuronal survival. Moreover, activated astrocytes producing B-cell activating factor (BAFF) could readily be envisioned to have a profound influence on levels of virus expression of Epstein-Barr virus harboring B cells recently recognized within leptomeningeal infiltrates within MS brain.

Demyelination is the cardinal feature of MS, but remyelination is also seen (see Figure 1). Within acute plaques remyelination can be found in the face of macrophages laden with myelin debris, and it appears that for at least 20% of MS patients remyelination can be extensive within the majority of their lesions; unfortunately, this is not the rule. What factors condition oligodendroglial cell precursors to migrate to areas of myelin disruption, proliferate, differentiate, contact denuded axons and lay down new myelin is increasingly yielding to reductionist neurobiological approaches.

Understanding whether and how to inhibit astrocytic production of a chemokine like CXCL1 (produced in reactive astrocytes and known to halt the migration of oligodendroglial precursor cells), might allow better migration of oligodendroglial cell precursors from normal tissues into plaques to better effect myelin repair. Learning how to enhance oligodendroglial cell precursor activation and attraction to sites of focal myelin injury with small molecules that partition well into brain could obviate any need for attempts at exogenous stem cell transfer experiments to facilitate better repair.

There is evidence that denuded axons are particularly vulnerable (see Figure 1). Sustained high firing rates in axons traversing demyelinated sections of spinal cord in the presence of low levels of nitric oxide results in conduction failure and can cause axonal death. The implications of these findings for generation of symptoms during acute attacks of multiple sclerosis, and accumulating sustained disability should be obvious. Low concentrations of sodium channel blockers antagonize much of the noxious effect of nitric oxide. There is some indication that this approach may lead to better axonal survival in experimental allergic encephalomyelitis, and the approach is being extended in clinical trials in multiple sclerosis.

Enlightened serendipity has spurred several therapeutic advances in multiple sclerosis. The development of glatiramer acetate reflects one such story. Another may be just now evolving. Fingolimod is an orally administered spingosine-1-phosphate (S1P) receptor modulator. S1P receptors are G coupled protein receptors involved in cell migration and vascular maturation. Once phosphorylated, fingolimod-P acts as a superagonist causing the aberrant internalization of S1P receptors of activated

Continued from page 4; Beierlein

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Bergmann glia (BG), a type of astrocyte found in cerebellar cortex, can influence synaptic transmission on rapid time scales. We examined changes in synaptic strength following brief stimulus bursts at parallel fiber (PF) synapses, which are formed by granule cells onto Purkinje neurons. These synapses are almost completely ensheathed by BG, making them a very promising potential target for gliotransmission. We found that activation of PF synapses with realistic stimulus bursts can evoke Ca2+ signals in BG lasting tens of seconds (Figure 1). These signals are triggered by the activation of metabotropic glutamate receptors as well as purinergic receptors expressed by BG, which in turn activate phospholipase C, the production of IP3 and ultimately the release of Ca2+ from internal stores.

Can Ca2+ signals in BG trigger release of a transmitter that modulates synaptic strength at nearby PF synapses? If so, its action would be mediated by the activation of presynaptic receptors, thereby altering evoked Ca2+ influx. To test this possibility, we loaded PFs with fluorescent Ca2+ indicators and then optically monitored evoked Ca2+ transients in PF terminals prior to and following a stimulus burst known to elicit Ca2+

responses in BG. In previous studies we have shown that such bursts of PF activity can lead to endocannabinoid release from Purkinje cells and GABA release from interneurons, leading to a decrease in presynaptic release probability via activation of cannabinoid and GABAB receptors, respectively. Importantly, both types of presynaptic modulation can be reliably detected by optically monitoring presynaptic Ca2+ influx, indicating that we have sufficient sensitivity to detect the potential modulation via a gliotransmitter. However, we found that PF activity that leads

to widespread Ca2+ signals in BG does not modulate presynaptic Ca2+ influx, under conditions where the activation of cannabinoid and GABAB receptors is prominent. Therefore, BG cells do not appear to release gliotransmitters that influence release probability on rapid time scales. It remains possible that calcium increases trigger long-term structural processes in BG such as changes in glial coverage of synapses, which could result in changes in synaptic efficacy.

Outlook There is little doubt that astrocytes can participate

in regulating synaptic transmission. However, our negative results add to the evidence for significant heterogeneity among astrocytes. Thus, findings derived from the hippocampal circuitry clearly do not generalize across different CNS synapses. Several key questions remain for future research: What are the molecular steps underlying transmitter release from astrocytes? Are astrocytes activated by neurons in vivo and if so, does the release of gliotransmitters from glia in vivo modulate synaptic transmission? And finally, do astrocytes play a role in information processing, learning and memory?

About the author:Michael Beierlein earned a Diploma in Biology at the University of Tübingen (Germany)

before receiving a Ph.D. in Neuroscience in the laboratory of Barry Connors at Brown

University. He then conducted postdoctoral research with Rafael Yuste at Columbia

University and with Wade Regehr at Harvard Medical School. He joined the Faculty of the

Department of Neurobiology and Anatomy as an Assistant Professor in the fall of 2007. His

research will focus on synaptic dynamics in neocortical circuits.

Volume 14, numBer 01 | Winter 20086

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lymphocytes. This deprives them of a critical signal required for their egress from lymph nodes and prevents their trafficking to target organs. In a phase 2 trial, fingolimod reduced the number of enhancements seen on serial MRI and clinical relapse rates of relapsing remitting MS patients. Fingolimod partitions well into brain, and the family of S1P receptors (S1P1 through S1P5) is also broadly expressed on oligodendroglial cells. Moreover, spingosine-1-phosphate S1P is involved in platelet-derived growth factor (PDGF)-induced upregulation of the delayed rectifier and regulation of Ca++ homeostasis, and in neurotrophin-3 signaling in oligodendroglial precursor cells, as well as in the proliferation of astrocytes and neural progenitor cells. The extent to which fingolimod’s presence in normal and affected tissues of MS brain might act to enhance or attenuate oligodendroglial cell regeneration and remyelination, alter the response of astrocytes within or about lesions, and effect neurons and their processes now requires intense scrutiny. Fortunately, early data from the study of animal models does not suggest any paradoxical detrimental effects. However dissecting the contribution of the anti-inflammatory and more direct neurotrophic benefits of fingolimod therapy illustrate the challenges of defining neuroprotection when a single drug potentially acts within both of these important organ systems.

The challenges to further advance therapeutics and multiple sclerosis must be solved at multiple levels inviting an ever increasingly close collaboration between neuroscientists and clinical trialists. While dissecting the potential dual actions and consequences of fingolimod might seem to represent a relatively unique problem, it is more indicative of what will be faced in

future trials. It is increasingly impossible to develop and test “pure” neuroprotectants for their effects in multiple sclerosis in isolation, as molecules designed to have selective effects only on glial and neuronal cells will need to be pursued as add-on therapy on the base of a best available immunomodulator. For the clinical trialists, we will need to be vigilant for unexpected drug-drug interactions that are antagonistic rather than additive or synergistic in such combination or add-on trials. We also need to learn how to more directly measure the effects of remyelination and axonal preservation with advanced multimodal MR imaging. Some of these issues can be addressed in part in animal models, but ultimately one must explore the human disease.

About the authorJerry S. Wolinsky, MD, is the holder of the Bartels Family and Opal C. Rankin Professorships

of Neurology at the UTHSC-Houston Medical School. He also is a faculty member of the

Graduate School of Biomedical Sciences at UTHSC-Houston and the director of the Multiple

Sclerosis Research Group and the Magnetic Resonance Imaging Analysis Center. Dr.

Wolinsky received his medical degree from The University of Illinois and did a residency in

clinical neurology, a fellowship in experimental neuropathology and faculty appointment at

The University of California San Francisco. While in San Francisco, his research interests

concentrated on the pathogenesis of viral infections of the nervous system, and his clinical

efforts began to focus on experimental therapeutics of infections of the central nervous system

and multiple sclerosis. He subsequently joined the faculty of The Johns Hopkins University

Schools of Medicine, and Hygiene and Public Health in 1978 before settling in Houston in

1983. In Baltimore, he applied more molecular tools to his basic investigations and became

more interested in the primary and secondary immunopathogenesis of neural disease. He

currently is active in the design, implementation, conduct, and analysis of clinical trials of

multiple sclerosis and conducts basic and applied research in quantitative magnetic resonance

imaging and magnetic resonance spectroscopic imaging in demyelinating diseases.

Figure 1: From Waxman, S.G., N. Engl. J. Med.:338:323, 1988.

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Ernst Knobil LectureThe Ernst Knobil Lecture was held on October 17, 2007 with Dr. Alfred Goldberg speaking on “Functions of the Proteasome: From Protein Degradation and Antigen Presentation to Cancer Therapy” Pictured from left to right are Dr. Giuseppe Colasurdo, Dr. Stanley Schultz, Dr. Heinrich Taegtmeyer, Dr. Alfred Goldberg, Dr. Julie Knobil, and Dr. John Byrne.

Neuroscience Research Center’s Distinguished LecturerThe NRC’s Distinguished Lecturer in 2007 was Dr. John Mazziotta of the UCLA Medical School. He spoke on October 11 on “Atlas of the Human Brain”. He is pictured here with Dr. Frank M. Yatsu of the Department of Neurology UTH Medical School, and Dr. Robert Grossman, chair of Neurosurgery at Methodist Hospital.

The Society for NeuroscienceThe annual Neuroscience Research Center (NRC) reception was held on November 6, 2007 at the Annual Meeting of the Society for Neuroscience (SfN) in San Diego, CA. The NRC had presented a poster on our Brain Week Activities at the Annual Dana Alliance Workshop which was held at SfN on November 3.

Brain Awareness MonthMayor Bill White has proclaimed March 2008 as Brain Awareness Month in Houston, Texas.

Non-Profit Org.

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Houston, TX

Permit No. 209

6431 Fannin, MSB 7.046Department of Neurobiology & AnatomyHouston, TX 77030

Questions? Comments? Contact us at 713-500-5540 or E-mail: nba-nrc@uth.tmc.edu

The Neuroscience Research Center NewsletterEditor David W. Marshak, Ph.D.

Assistant Editor Margaret R. Clarke, Ph.D.

Design Lorenzo Morales

Editorial Board Ian J. Butler, M.D.; Raymond J. Grill, Ph.D.; Stephen Mills, Ph.D.; Andrew C. Papanicolaou, Ph.D.;

Alan C. Swann, M.D.; Jack C. Waymire, Ph.D.; Frank M. Yatsu, M.D.

The Neuroscience Research CenterA Component of The University of Texas

Health Science Center at Houston

Director John H. Byrne, Ph.D.

Executive Committee Peter J. Davies, M.D.,Ph.D., Ex-Officio; Louvenia Carter-Dawson, Ph.D.; Pramod Dash, Ph.D.; Linda Ewing-Cobbs, Ph.D.; James A. Ferrendelli, M.D.;

Ralph Frankowski, Ph.D.; James C. Grotta, M.D.; Robert W. Guynn, M.D.; F. Gerard Moeller, M.D.; Ponnada A. Narayana, Ph.D.; Alex Valadka, M.D.

The University of Texas Health Science Center at HoustonPresident James T. Willerson, M.D.