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INSC 587

INSC 587 NEUROBIOLOGY OF DISEASE

SYLLABUS and OUTLINE OF STUDENT PRESENTATIONS

Instructor: Dr. Marc Dichter (349-5166; dichter@mail.med.upenn.edu)

Time: Fall, 2007, Tuesday afternoon - 4:00 - 5:30 PM

Thursday afternoon - 4:00 - 5:00 PM

Room: Barchi Library, 140 John Morgan Building

Textbook: There is no one text suitable for the course. Readings will be assigned for each class and more in depth bibliographies will be developed for each topic. Many of the chapters in “The Molecular and Genetic Basis of Neurological Disease” edited by Roger Rosenberg, Stanley Pruisiner, Salvatore DiMauro, and Robert Barchi, Edition 2 or 3, are a good initial source. Copies are available on reserve in the medical library and in the Neuroscience library.

Activities for which students will prepare in advance of class:

For student-led activities the class will be divided into two teams. For each activity, two members from each team will sign up to take primary responsibility for their team’s presentation. The other members of each team will be responsible for assisting their team members and for answering questions during the discussion.

Discussion of clinical trials papersAll students will read a paper(s) describing the results of a clinical trial(s) for a given disease. After the designated students from each team present their paper, other team members will compare and contrast “their team’s paper” with the paper presented by the other team.

Debate on alternative mechanismsStudents will read papers given evidence in support of a particular mechanism as central to the etiology of a given disorder. Members of opposing teams will read papers supporting different mechanisms. The two designated members of each team will present the best evidence in support of “their” mechanism, then other team members may present a rebuttal of points argued by the opposing team.

Presentation on caregiver issues Two students, one from each team, will work together to prepare a  presentation on the psychological, financial, logistic, etc. issues faced by caregivers of persons with AD or PD or other long-term neurodegenerative disorders.

Website review All students will review a website relevant to a particular disorder and write a 1 page summary written of what impressed them most.

Grading - Grades for the course will be based on presentation(s), written assignments, and ability to answer questions and participate in the discussions during class.

Week #

TUESDAY

Lecturer

THURSDAY

Lecturer

1

Sept 11

Mechanisms of brain dysfunction (Dichter)

Necrosis vs apoptosis or how cells die (Neumar)

Dichter / Neumar

Sept 13

NO CLASS - Rosh Hashonah

2

Sept 18

Stroke and ischemic brain damage

PATIENT PRESENTATION

Student review of one Stroke website in advance of class. Students will turn in at the start of class a written 1 page (single spaced) summary of what impressed them most from one of these websites:

www.strokeassociation.org;

www.stroke.org;

www.strokecenter.org

Dichter

Sept 20
Regulation of NMDA receptor function and excitotoxicity

Lynch

3

Sept 25

Alzheimer’s Disease

Debate: Amyloid hypothesis vs tau hypothesis vs synaptic dysfunction preceeding pathology – from mouse studies

Dichter

Sept 27

Overview of clinical trials: acute and chronic

Balcer

4

Oct 2

ALS & what familial forms of genetic disease can and cannot tell us about the sporadic cases

Debate: Can or cannot familial forms of a disease provide clues about the etiology of the sporadic cases?

  • Trojanowski/Lee 2007 paper on ALS sporadic and familial forms

Dichter

Oct 4

Student Presentation of Clinical Trials for ALS

  • Team 1- A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis;Bensimon et al, 1994NEJM
  • Team 2- A controlled trial of recombinant methionyl human BDNF in ALS 1999Neurology

5

Oct 9

Schizophrenia

Debate: A developmental disease vs a dysfunction of the dopaminergic system?

Development disease papers:

  • Investigating the neurodevelopmental hypothesis of schizophrenia, Rehn et al, Clin&ExpPharm2005
  • Overview of neuropathological theories of schizophrenia: from degeneration to progressive developmental disorder. de Haan et al Psychopathology2004

Dysfunction of DA (and GLU) system papers:

  • TBD

Gur

Oct 11

Animal models of psychiatric disorders and the  

role of endophenotypes

Bucan

6

Oct 16

Huntington’s Disease and other triplet repeat diseases. How repeats in untranslated regions can cause disease?

Student Presentation on Caregiver Issues
Website research: Impact of foundations on research

Specific website links and some helpful questions will be provided.

Lynch

Oct 18

Using simple biological models for neurodegenerative diseases

Gitler

7

Oct 23

Parkinson’s Disease

Student Presentation of Clinical Trials for PD

  • DATATOP: a multicenter controlled clinical trial in early Parkinson's disease. Arch Neurol1989
  • CALM-PD: Pramipexole vs levodopa. Two papers on the same trial: JAMA2000 and Arch Neurol2004

Lynch

Oct 25

Mitochondrial dysfunction in neurodegenerative disease

Rob Wilson

8

Oct 30

Epilepsy - seizure mechanisms

PATIENT PRESENTATION

Dichter

Nov 1

Mechanisms of epileptogenesis

Debate: does preventing damage prevent epilepsy?

  • Papers TBD

Coulter?

9

Nov 6

NO CLASS - SfN:meeting is Nov 3-7

Nov 8

Depression / Affective Disorders and disorders with complex genetics

Debate: GABA hyp vs. serotonin hyp

(or maybe include NE and/or DA)

  • Papers TBD

TBD

10

Nov 13

Overview of interactions between immune and nervous systems; autoimmune disorders

PATIENT PRESENTATION?

Student review of MS Society website in advance of class.

Kariko

Nov 15

Multiple Sclerosis

Student Presentation of Clinical Trial for MS:

  • Tysabri
  • Retuximide

Dichter

11

Nov 20

Diseases of Peripheral Nerve; finding the causes of peripheral neuropathies; Charcot-Marie Tooth

Scherer

Nov 22

NO CLASS – Thanksgiving

12

Nov 27

Disorders of brain development – from learning disabilities to mental retardation; aberrant gene expression during development

Crino

Nov 29

Autism, Asberger’s and other autism spectrum disorders. Use of twin studies in complex disorders such as schizophrenia and autism, assessing cognitive function in autistic kids

Debate: social construct theory vs genetics theory vs vaccine theory vs environmental theory.

Brodkin

13

Dec 4

How do mutations in widely expressed proteins lead to degeneration or dysfunction of small subsets of neurons?

Student led discussion of several hypotheses

Taylor

Dec 6

Macular degeneration

Dunaief