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NEU 221: Animal Models of Degeneration and Regeneration in the CNS

Winter quarter, 2007


Instructors: David Kang and Binhai Zheng

Place: Leichtag Biomedical Research Building, Room 2A05

Time: 1 - 3 pm every Tuesday (1/9/07 - 3/13/07)

Course descriptions: This course will include discussions on selected papers in degeneration and regeneration of the mammalian central nervous system that utilize animal models to address molecular and cellular mechanisms. Each student is assigned one or more seminal/important research papers to present. All students are expected to read assigned background materials and research papers in advance in order to engage actively in the discussions. Topics to be addressed will include Alzheimer's, Parkinson's, frontotemporal dementia, ALS, spinal cord injury, among others. Students in all graduate and medical programs with the appropriate background are encouraged to register. Some background knowledge in molecular and cellular biology, biochemistry, genetics and neurobiology is expected.


Session 1 (1/9/07): Introduction to the course & selection of topics

Session 2 (1/16/07): Animal models of Alzheimer's disease (AD) Dan Darcy

Review1: A decade of Modeling Alzheimer's disease in transgenic mice

Review2: The cell biology of Alzheimer's disease: uncovering the secrets of secretases

Article1: Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein

Article2: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction

Session 3 (1/23/07): Alzheimer’s disease and tauopathies (continued) Audrey Oneill

Review: Mutations causing neurodegenerative tauopathies

Article1: Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein

Article2: Tau suppression in a neurodegenerative mouse model improves memory function

Session 4 (1/30/07): Animal models of Parkinson’s disease (PD) Dustin Wakeman

Review: Parkinson's disease: a rethink of rodent models

Article1: alpha -Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's Disease

Article2: Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein

Supplemental review: Neural repair strategies for Parkinson's disease: insights from primate models

Session 5 (2/6/07): Animal models of Amyotrophic Lateral Sclerosis (ALS) Andrew Crain

Review: Unraveling the mechanisms involved in motor neuron degeneration in ALS

Article1: Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice

Article2: Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model

Session 6 (2/13/07): Wallerian degeneration (Wlds model) Ann Shih

Review: Tracking in the Wlds--the hunting of the SIRT and the luring of the Draper

Article1: Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration

Article2: NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration

Session 7 (2/20/07): CNS axon regeneration I: the glial scar and the CSPGs Jiun Do

Review: Regeneration beyond the glial scar

Article 1: Chondroitinase ABC promotes functional recovery after spinal cord injury

Article 2: Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury

Session 8 (2/27/07): CNS axon regeneration II: myelin-derived inhibitors of neurite outgrowth Eunice Chen and Renee Chow

(2/27/07): CNS axon regeneration II: myelin-derived inhibitors of neurite outgrowth

Review: Glial inhibition of CNS axon regeneration

Article 1: Axon regeneration in young adult mice lacking Nogo-A/B

Article 2: Lack of enhanced spinal regeneration in Nogo-deficient mice

Article 3: Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury

Supplemental review: Genetic mouse models for studying inhibitors of spinal axon regeneration

Session 9 (3/6/07): Stem cells I: adult stem cells (in spinal cord injury model) Nick Wall

Review: The therapeutic potential of neural stem cells

Article 1: Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome

Article 2: Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice

Session 10 (3/13/07): Stem cells II: embryonic stem cells (in Parkinson’s model) Lara Rangel

Review: Stem and progenitor cell-based therapy of the human central nervous system

Article 1: Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Article 2: Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. If this link does not work, try this direct link to full journal article.