Neurobiology of Disease

 


 
 
  Themes 2009

Introduction

The neurobiology of disease refers to fundamental genetic, molecular, cellular, systems, and behavioral abnormalities that contribute to the manifestations of disease. From a practical perspective, disease-oriented research is not necessarily the same thing as the currently popular term, translational research. Any research that is directed at a specific disease or disease manifestation is often called "translational", but NIH has a more narrow definition i.e. any research that involves human subjects or that has immediate application to clinical therapies (e.g. clinical trials). Unfortunately, many areas of neurological and psychiatric disease still lack the fundamental insights or technology required for therapeutic application. Likewise, there are many examples where "undirected" basic research has led to clinical breakthroughs. Thus in neuroscience there is room (and great need) for both basic research as well as translational research. The introductory session overviews this spectrum, beginning with a discussion of neurobiological mechanisms that underlie neuropsychiatric disease. A clinical session will introduce the practical aspects of how neurological diagnoses are made.

This course is a "sampler" so participants should not expect to walk away with a comprehensive understanding on any one disease or disease mechanism, but rather we hope to impart an appreciation of the impact of disease on patients, and an understanding of the potential links between basic science and disease mechanisms.

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Neurodegeneration (ALS and Alzheimerís disease)

This theme will examine topical issues in neurodegenerative disease, using amyotrophic lateral sclerosis and Alzheimer's disease as the focal points this year. We will interview patients with ALS and Alzheimer's following sessions that overview the clinical and potential mechanism of these diseases. We will also discuss the concept of "selective vulnerability" in neurodegenerative disease and consider the value of various animal models in exploring mechanisms of neurodegeneration. Three visiting experts (Joe Beckman (Oregon State), Don Cleveland (UCSD) and David Holtzman (Washington University) will also provide their perspectives on the current state of research in ALS and Alzheimerís disease, respectively.

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Sensory failure (hearing loss)

Deafness and blindness are common causes of neurological disability. This theme will begin with an overview of the common types of hearing loss and their proposed mechanisms, both acquired and genetic. The session will benefit from presenters who themselves have hearing loss. We will also discuss one of the most successful prosthetic devices in clinical use - the cochlear implant. Finally, in a journal club format we will explore recent studies aimed at some of the genetic mechanisms underlying hearing loss.

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Axonal degeneration (MS)

This theme will examine the mechanisms of axonal degeneration, which are manifest in a number of neurological diseases. Our clinical focus for this theme will be multiple sclerosis (MS). Sessions on MS will include a clinical overview of the disease and it treatment, and we will interview a patient with MS. We will also discuss methods of early or pre-clinical diagnosis and their role in testing treatments that might be most effective early in the course of the disease. Experimental autoimmune encephalomyelitis (EAE) has been used as a model of MS Ė we will discuss its benefits and limitations and explore an example where EAE has led to current clinical trials of potential therapies. During the second week of this theme, students will attend the 2009 Jungers Center symposium on Axonal Degeneration (see www.ohsu.edu/jungers), which features outside 4 experts discussing recent research on this topic. The theme will conclude with a debriefing of the issues raised by the symposium.

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Dopamine systems (Parkinsonís disease and substance abuse)

Dopamine systems control both motor and non-motor aspects of behavior. When these systems co awry because of degeneration or maladaptive plasticity, movement disorders or addictive behaviors occur. We will focus on the role of dopamine systems in Parkinsonís disease and the role of dopamine in abnormal behaviors in the reward circuitry. The theme will include an overview of Parkinsonís disease and a patient interview. Charles Wilson (UT San Antonio) will discuss the cellular and circuit abnormalities in the basal ganglia that underlie disorders of dopamine systems. In the final session, we will examine the role of exogenous dopamine in triggering maladaptive plasticity and addictive behavior.

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Clinical Rounds

During this week students will be matched for a 1/2 day with a clinician on the inpatient wards, the neuroscience intensive care unit or one of the subspeciality neurology clinics. This opportunity will allow students to see how neurological health care is delivered and some of the issues that face patients and clinicians on day-to-day basis. In the final session of this theme, we will share the experiences of the week.

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