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
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.
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.
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.
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.
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.