Course Proposal for USC Neuroscience Graduate Program
version 11-15-08
Department of Neurology
Keck School of Medicine at USC
Title
Neurobiology of Disease II (currently BISC 599)
Time and Location
Thursdays 9:00 am -12:00 pm Spring Semester starting January 15, 2009 to April 30, 2009.
The class will meet on the HSC campus in van der Meulen Library HCCII Suite 3000, number 3223.
The HCCII building is located at 1520 San Pablo St right across the street from the Zilkha Neurogenetics
Institute.
Instructors
The course directors will be Michael Jakowec, PhD, Giselle Petzinger, MD, and Andres Gonzalez, MD,
from the Department of Neurology. Professors’ hours for discussions can be made by appointment or
Thursdays from 1 to 4.
Contact:
Michael Jakowec, PhD, mjakowec@surgery.usc.edu (323) 442-1057
MCA-241
Giselle Petzinger , MD, gpetziger@surgery.usc.edu (323) 442-1057
MCA-243
Andres A Gonzalez, MD, andresgo@usc.edu (323) 442-8852
DEI- 2500
Overview
The purpose of this course is to provide a basic introduction to the fundamental aspects of common
diseases affecting the brain. These disorders include Parkinson’s disease (PD), Alzheimer’s disease (AD),
Multiple Sclerosis (MS), epilepsy, pain, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD),
neuromuscular disorders, and stroke. During this course students will gain an appreciation for the utility of
animal models of human neurological disorders, gain some understanding of the clinical presentation and
current understanding of these disorders, and begin to appreciate important aspects of these disorders
including the role of the immune system, the genetic basis of many disorders, and the links between neuronal
dysfunction and neuropathology. The instructors will open and close each session with highlights of the
disorder, the objectives of the presentation, and what was learned in the session linking our understanding to
other neurodegenerative disorders already studied. This will allow central themes to be developed and an
understanding of the potential mechanisms that link these different disorders. A major goal is to develop an
interest and understanding of the opportunities and challenges to translational medicine, linking basic and
clinical research.
Prerequisites
This course will be limited to graduate students in the Neuroscience Graduate Program, Senior
undergraduates, postdoctoral fellows, clinical residents, clinical fellows, and graduate students from other
programs. The topics of each class will be circulated to other faculty who may choose to attend and enrich the
discussions. Students will be expected to have taken NEUR524 or an equivalent introductory course in the
Neuroscience Graduate Program core. While the instructors will cover basic aspects of introduction to each
disorder, students should have a elementary understanding of neuroanatomy, neurophysiology, cell biology,
and biochemistry.
Course Format
This course will be in the format of a directed seminar/lecture under the guidance of the instructor for
the specific session. IN many sessions there will be multiple instructors and other faculty with specific interests
of the topics under discussion are invited to attend and actively participate and stimulate discussions. During
each 3 hour weekly session the instructor will engage the students with questions and draw comments or
interpretations primarily based on the assigned reading. Students are expected to ask questions and
participate in an interactive fashion.
Course Outline
(1) A lecture and discussion course
(2) Maximum of 24 students.
(3) Suggesting readings will include a combination of one classic paper, one “cutting edge” recent paper and
one review article. However, in some sessions such as during the first semester the reading will consists of
specific chapters from a recommended (not mandatory) textbook.
(4) Grading is based on class participation, attendance, discussion, and a term paper.
Each lecture will consists of a 3-hour period whose formal presentation and discussion will be led by a
faculty member whose expertise is in one or more of the common disorders covered in this course. Some
topics will be divided based on either the basic or clinical perspective but this is at the discretion of the teamed
instructors. Each faculty member who leads a class will be expected to cover specific aspects of the disorder
including anatomical correlates, clinical features, etiology, epidemiological issues, genetics, cellular and
molecular biology of affected cell groups, imaging, animal and cellular models, treatments, and highlights of
ongoing and future research. While this may seem like a vast amount of information for students it is the
intention of the instructors to synthesize a vast body of information and data, express the opinions of the field
and identify critical topics or debates that dominate the field. The instructor may also prepare a handout or
make available slide sets via the web consisting of relevant figures and visual aids. The instructor will
assemble a reading list consisting of required reading prior to attending the class. The instructor will also
suggest specific references to additional topics that may be of interest to students who may want to investigate
a subject more thoroughly. This reading list may also serve as a basis for students to gain additional
information of topics of interest relevant to each disorder as part of their preparation for a term paper.
To assist with the continuity between class sessions and topics the course instructors Drs. Petzinger,
Gonzales, and Jakowec, as the supervisors of this course, will attend all classes. A strength of this course is
the fact that the faculty who lead the sessions are themselves directly involved in either or both basic and
clinical research or clinical care of patients with these important neurodegenerative disorders.
Rationale: There is a fundamental need for graduate students in the NGP and other programs, clinical fellows
and residents to obtain a basic understanding of human neurodegenerative disorders. The purpose of this
course is to provide an introduction to diseases including PD, AD, ALS, MS, stroke, neuromuscular, and others
from the prospective of current basic mechanistic understanding, research directions, clinical features and
treatment and future research directions. In the most recent UCAR review, as well as a recent Deans and
Provost Neuroscience Advisory Group (DPNAG), the review committee highlighted the need for greater
emphasis on translational medicine linking basic and clinical research, as well as the need to better integrate
the HSC with the UPC neuroscience programs. This proposed lecture course is a direct response to this need
as well as a reflection of the enthusiasm of the faculty of Neurology to be involved in teaching at the graduate
student level.
Syllabus The topics to be covered and lead faculty are the following. Some faculty may bring in additional
resources including videos, adjunct faculty, or patients.
Spring Semester 2009
Session Date
Topics and
Instructors
Parkinson’s Disease (2 Class Sessions)
Session 1
Michael Jakowec, PhD
January 15,
Giselle Petzinger, MD
2009
Session 1
Michael Jakowec, PhD
January 15,
2009
Session 2
January 22,
2009
Giselle Petzinger, MD
Alzheimer’s Disease (2 Class Sessions)
Session 3
Helena Chui, MD
January 29,
2009
Session 4
Roberta Brinton, PhD
February 5,
2009
Multiple sclerosis (2 Class Sessions)
Session 5
Brett Lund, PhD
February 12,
2009
Session 6
Wendy Gilmore, PhD
February 19,
2009
Epilepsy (2 Class Sessions)
Session 7
Elyse Schauwecker,
February 26,
PhD
2009
Session 8
Laura Kalayjian, MD
March 5, 2009
Pain (1 Class Session)
Session 9
David McKemy, PhD
Topics to be Covered
Suggested Readings for Each Session
Introduction
to
Neurodegenerative Disorders
Anatomy of the basal ganglia;
neurotransmitter
systems
important to PD; molecular
correlates; animal models of
PD; genetics of PD, strategies
for dopamine replacement
including engineered vectors
and stem cells.
Clinical
features;
neuroplasticity in PD and its
models;
electrophysiological
studies; treatment strategies
and
translational
studies;
modifying disease progression;
neuro-imaging.
A. Parent and L. N. Hazrati (1995) Functional anatomy of the basal
ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. 20, 91-127,
(1995) Functional anatomy of the basal ganglia. II. The place of
subthalamic nucleus and external pallidum in basal ganglia circuitry. 20,
128-154,A. R. Crossman (2000) Functional anatomy of movement
disorders. 196, 519-525,P. Greengard (2001) The neurobiology of
dopamine signaling. 21, 247-269,M. W. Jakowec and G. M. Petzinger
(2004) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned model of
parkinson's disease, with emphasis on mice and nonhuman primates. 54,
497-513,M. J. Hurley and P. Jenner (2006) What has been learnt from
study of dopamine receptors in Parkinson's disease? 111, 715-728.
O. Hornykiewicz (1998) Biochemical aspects of Parkinson's disease. 51,
S2-S9,S. Fahn and S. Przedborski (2000) Parkinsonism. 679-693,F.
Coppede, M. Mancuso, G. Siciliano, L. Migliore and L. Murri (2006) Genes
and the environment in neurodegeneration. 26, 341-367,Z. Israel and H.
Bergman (2007) Pathophysiology of the basal ganglia and movement
disorders: From animal models to human clinical applications. .
Clinical
features;
current
treatments; the debate on AD,
genetics of AD.
Pharmacological approaches
for treatment
Cummings JL, Doody R, Clark C. Disease-modifying therapies for
Alzheimer disease: challenges to early intervention.Neurology. 2007 Oct
16;69(16):1622-34. Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A.
Neuroinflammation in Alzheimer's disease and Parkinson's disease: are
microglia pathogenic in either disorder? Int Rev Neurobiol. 2007;82:23546. Solomon B. Antibody-mediated immunotherapy for Alzheimer's
disease.
Curr Opin Investig Drugs. 2007 Jul;8(7):519-24. Ertekin-Taner N. Genetics
of Alzheimer's disease: a centennial review.
Neurol Clin. 2007 Aug;25(3):611-67. Reid PC, Urano Y, Kodama T,
Hamakubo T. Alzheimer's disease: cholesterol, membrane rafts,
isoprenoids and statins. J Cell Mol Med. 2007 May-Jun;11(3):383-92.
Wang JM, Irwin RW, Brinton RD. Activation of estrogen receptor alpha
increases and estrogen receptor beta decreases apolipoprotein E
expression in hippocampus in vitro and in vivo. Proc Natl Acad Sci U S A.
2006 Nov 7;103(45):16983-8. Brinton RD.Impact of estrogen therapy on
Alzheimer's disease: a fork in the road? CNS Drugs. 2004;18(7):405-22.
The immune system,
1.
Neuroimmunology, immune
system and disease.
Clinical features of MS,
molecular features of MS;
neuroanatomy and
Bernard Hemmer, Stefan Nessler, Bernd Kieseier and Hans-Peter
Hartung. Immunopathogeneis and immunotherapy of multiple sclerosis.
Nature Clinical Practice 2:201, 2005.Hans Lassmann, Wolfgang Bruck and
Claudia F. Lucchinetti. The immunopathology of multiple sclerosis: An
overview. Brain Pathology 14:210, 2007. Stephen L. Hauser and Jorge R.
Oksenberg. The neurobiology of multiple sclerosis: Genes, inflammation
and neurodegeneration. Neuron 52:61, 2006. Larry Steinman and Scott
Zamvil. How to successfully apply animal studies in experimental allergic
encephalomyelitis to research on multiple sclerosis. Ann Neurol. 60:12,
2006.
Animal models; mechanisms
of
cell
death;
plasticity;
genetics.
Clinical
features;
current
treatments;
clinical
trials;
genetics, gender, and age;
Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg
Drugs. 2007 Sep;12(3):407-22. Shetty AK, Hattiangady B. Concise review:
prospects of stem cell therapy for temporal lobe epilepsy. Stem Cells.
2007 Oct;25(10):2396-407. M, Schoch S, Lie A, Becker AJ. Molecular
neuropathology of temporal lobe epilepsy: complementary approaches in
animal models and human disease tissue. Epilepsia. 2007;48 Suppl 2:412. Aronica E, Gorter JA. Gene expression profile in temporal lobe
epilepsy. Neuroscientist. 2007 Apr;13(2):100-8. Baraban SC. Emerging
epilepsy models: insights from mice, flies, worms and fish. Curr Opin
Neurol. 2007 Apr;20(2):164-8. Berkovic SF, Mulley JC, Scheffer IE, Petrou
S. Human epilepsies: interaction of genetic and acquired factors. Trends
Neurosci. 2006 Jul;29(7):391-7.
Animal
Takasima et al (2007) Diversity in the neural circuitry of cold sensing
models,
molecular
March 12
2009
mechanisms,
correlates.
Spring Recess
March 19,
2009
Stroke (1 Class Session)
Session 10
Nerses Sonossian,
March 26,
MD
2009
NO CLASS
ALS, SMA, MND (2 Class Sessions)
Session 11
Michael Jakowec,
April 2, 2008
PhD
Chien-Ping Ko, PhD
Session 12
Said Beydoun, MD
April 9, 2008
clinical
revealed by genetic axonal labeling of transient receptor potential
melastatin 8 neurons. J Neurosci. 27(51):14147-57. McKemy (2005) How
cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Mol
Pain. 1:16.
Clinical features; imaging;
treatments;
clinical
trials,
animal models, preclinical
studies.
Cimino M, Gelosa P, Gianella A, Nobili E, Tremoli E, Sironi L. Statins:
multiple mechanisms of action in the ischemic brain. Neuroscientist. 2007
Jun;13(3):208-13. Curtis MA, Eriksson PS, Faull RL. Progenitor cells and
adult neurogenesis in neurodegenerative diseases and injuries of the
basal ganglia. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):528-32.
Lapchak PA, Araujo DM. Advances in ischemic stroke treatment:
neuroprotective and combination therapies. Expert Opin Emerg Drugs.
2007 Mar;12(1):97-112. Tonk M, Haan J. A review of genetic causes of
ischemic and hemorrhagic stroke. J Neurol Sci. 2007 Jun 15;257(1-2):2739. Nudo RJ. Postinfarct cortical plasticity and behavioral recovery.
Stroke. 2007 Feb;38(2 Suppl):840-5. Fisher M, Henninger N.
Translational research in stroke: taking advances in the pathophysiology
and treatment of stroke from the experimental setting to clinical trials. Curr
Neurol Neurosci Rep. 2007 Jan;7(1):35-41. Mitsios N, Gaffney J, Kumar
P, Krupinski J, Kumar S, Slevin M. Pathophysiology of acute ischaemic
stroke: an analysis of common signalling mechanisms and identification of
new molecular targets. Pathobiology. 2006;73(4):159-75.
Animal models; molecular
features;
role
immune
response; novel treatments.
Clinical
features;
current
treatments; electrophysiology;
motor neuron cell death.
Schymick JC, Talbot K, Traynor BJ. Genetics of sporadic amyotrophic
lateral sclerosis. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R233-42.
Hedlund E, Hefferan MP, Marsala M, Isacson O. Cell therapy and stem
cells in animal models of motor neuron disorders. Eur J Neurosci. 2007
Oct;26(7):1721-37. Bhatt JM, Gordon PH. Current clinical trials in
amyotrophic lateral sclerosis. Expert Opin Investig Drugs. 2007
Aug;16(8):1197-207. Martin LJ. Transgenic mice with human mutant
genes causing Parkinson's disease and amyotrophic lateral sclerosis
provide common insight into mechanisms of motor neuron selective
vulnerability to degeneration. Rev Neurosci. 2007;18(2):115-36.
Shoesmith CL, Strong MJ. Amyotrophic lateral sclerosis: update for family
physicians. Can Fam Physician. 2006 Dec;52(12):1563-9.
Gonzalez de Aguilar JL, Echaniz-Laguna A, Fergani A, Rene F, Meininger
V, Loeffler JP, Dupuis L. Amyotrophic lateral sclerosis: all roads lead to
Rome. J Neurochem. 2007 Jun;101(5):1153-60. Shaw BF, Valentine JS.
How do ALS-associated mutations in superoxide dismutase 1 promote
aggregation of the protein? Trends Biochem Sci. 2007 Feb;32(2):78-85.
Huntington’s Disease (1 Class Session)
Session 13
Dan Togasaki, Clinical
features;
history;
April 16, 2009
MD/PhD genetics, therapeutic
John Walsh PhD Animal models; mechanisms
of cell death and dysfunction;
Neuromuscular Disorders (2 Class Sessions)
Session 14
Valerie Askanas, MD Models, mechanisms, overlap
April 23, 2009
with central disorders.
Session 15
King Engel, MD Clinical features, diagnosis,
April 30, 2009
current
treatments,
future
therapeutic targets.
Session 15
April 30, 2009
Michael Jakowec,PhD
Giselle Petzinger, MD
Overview and highlights of the
course (remaining 45 minutes)
Wright BL, Barker RA. Established and Emerging Therapies for
Huntington's Disease. Curr Mol Med. 2007 Sep;7(6):579-87. Ramaswamy
S, Shannon KM, Kordower JH. Huntington's disease: pathological
mechanisms and therapeutic strategies. Cell Transplant. 2007;16(3):30112. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev
Neurosci. 2007;30:575-621. Walker FO. Huntington's Disease. Semin
Neurol. 2007 Apr;27(2):143-50. Nakamura K, Aminoff MJ. Huntington's
disease: clinical characteristics, pathogenesis and therapies. Drugs Today
(Barc). 2007 Feb;43(2):97-116.
Walker FO. Huntington's disease. Lancet. 2007 Jan 20;369(9557):218-28.
Askanas V, Engel WK. Inclusion-body myositis, a multifactorial muscle
disease associated with aging: current concepts of pathogenesis. Curr
Opin Rheumatol. 2007 Nov;19(6):550-9. Askanas V, Engel WK. Inclusionbody myositis: a myodegenerative conformational disorder associated with
Abeta, protein misfolding, and proteasome inhibition. Neurology. 2006 Jan
24;66(2 Suppl 1):S39-48. Rodino-Klapac LR, Chicoine LG, Kaspar BK,
Mendell JR. Gene therapy for duchenne muscular dystrophy: expectations
and challenges. Arch Neurol. 2007 Sep;64(9):1236-41. Schmid A,
DiDonato CJ. Animal models of spinal muscular atrophy. J Child Neurol.
2007 Aug;22(8):1004-12. Sumner CJ.
Molecular mechanisms of spinal muscular atrophy. J Child Neurol. 2007
Aug;22(8):979-89. Navarro X, Vivo M, Valero-Cabre A. Neural plasticity
after peripheral nerve injury and regeneration. Prog Neurobiol. 2007
Jul;82(4):163-201.
Summary of common themes linking many of the disorders covered; gaps
in our knowledge, future research and the prospects of translational
research.
Evaluation for student grades: Spring Semester
Students enrolled in this course will be graded. Evaluation of student performance will be based on
attendance, participation, and final written paper.
20% class participation: On a scale of 100, 0-indicating no participation, 100-indicating best participation.
The participation scores from all of the sessions will be averaged to obtain the aggregate participation score.
Participation will include asking and answering questions and being actively involved in the discussion. It is
expected that the students read the assigned papers prior to the lecture and be prepared to discuss
background, what was not known, what the question of the paper was, what they did experimentally in general
(methods), what the results are and what they mean (know the results!), what the weaknesses are, conclusion
of the paper.
80% term paper: A term paper of the students choosing is to be submitted by the end of the course. The term
paper may be structured as a critical evaluation of a specific basic or clinical topic relevant to one of the
disorders in the course, or the identification of a key question and papers that critically address the topic. Two
instructors, including one of the primary course directors, will critically evaluate the submitted paper. Students
will also be asked to complete an anonymous critical evaluation of the course itself. The paper will be due on
the last day of the course and will be a minimum of 10 pages with appropriate references.
Statement for Students with Disabilities
Any student requesting academic accommodations based on a disability is required to register with Disability
Services and Programs (DSP) each semester. A letter of verification for approved accommodations can be
obtained from DSP. Please be sure the letter is delivered to me (or to TA) as early in the semester as possible.
DSP is located in STU 301 and is open 8:30 a.m.–5:00 p.m., Monday through Friday. The phone number for
DSP is (213) 740-0776.
Statement on Academic Integrity
USC seeks to maintain an optimal learning environment. General principles of academic honesty include the
concept of respect for the intellectual property of others, the expectation that individual work will be submitted
unless otherwise allowed by an instructor, and the obligations both to protect one’s own academic work from
misuse by others as well as to avoid using another’s work as one’s own. All students are expected to
understand and abide by these principles. Scampus, the Student Guidebook, contains the Student Conduct
Code in Section 11.00, while the recommended sanctions are located in Appendix A:
http://www.usc.edu/dept/publications/SCAMPUS/gov/. Students will be referred to the Office of Student Judicial
Affairs and Community Standards for further review, should there be any suspicion of academic dishonesty.
The Review process can be found at: http://www.usc.edu/student-affairs/SJACS/.