Lecture Outline
Lecture 1. Introduction to Neurobiology of Disease
Defining the sequential cellular components of a disease process; interpreting the validity of experimental models; overview of developmental gene models of nervous system disease.
Module I. Development
Lecture 2. Disorders of migration and synaptogenesis
Vulnerable steps in brain development as revealed by mutational analysis. Cell cycle, fate determination, and migration from cortical proliferative zones; cortical lamination and role of radial glia, gliogenesis and myelination; synaptic targeting.
Lecture 3. Activity-dependent plasticity in developing neural circuits
Maturation of membrane excitability properties; role of firing pattern in synaptogenesis; abnormal cell migration, sprouting, and connectivity following neonatal seizures.
Lecture 4. Glial-neuronal interactions in development
Vulnerable steps in myelination, trophic interactions between nerve and oligodendrocyte and Schwann cell, glial modeling of axonal excitability, neurobiology of glial disease phenotypes in man and mouse.
Module II. Excitability
Lecture 5. Ion channel diseases I
Molecular biology, genetics, and physiology of sodium and calcium ion channel diseases in nerve and muscle.
Lecture 6. Ion channel diseases II
Molecular biology, genetics, and physiology of potassium and chloride ion channel diseases in nerve and muscle.
Lecture 7. Mechanisms of excitotoxicity.
Membrane receptors and intracellular events leading to depolarization-induced injury and cell death.
Lecture 8. Basic mechanisms of epilepsy
Genes and molecular mechanisms regulating abnormal synchronization in the CNS.
Module III. Death
Lecture 9. Molecular mechanisms of programmed cell death
Genes and proteins mediating apoptosis; the ced3-ICE connection; molecular inhibition of apoptosis; the ced9-BCL2 connection; BCL2 related proteins.
Lecture 10. Neurodegeneration in Alzheimer's disease
Molecular mechanisms and experimental models of Alzheimer's cytopathology. Apolipoprotein E, tau, and autoimmune mediated mechanisms of cell death.
Lecture 11. Genetic mechanisms of neuronal degeneration
Molecular genetics and cell biology of human triplet repeat mutations underlying neuronal cell death.
Lecture 12. Molecular signaling and muscular dystrophy
Molecular biology of dystrophin and biological phenotypes of the muscular dystrophies.
Lecture 13. Molecular mechanisms of deafness
Ultrastructure of the outer hair cell. Mutational analysis of cytoskeletal and membrane wall proteins associated with deafness. Molecular mechanisms of damage releated to hearing loss.
Module IV. Repair
Lecture 14. Neurotrophins and neural regeneration
Molecular biology of growth factors and their signaling pathways, role in cell survival, neuroprotection, and neosynaptogenesis.
Lecture 15. Gene therapy in the nervous system
Neural transplantation, transfection, and expression of transgenes. Modification of the diseased or traumatized nervous system using genetically engineered cell grafts; strategies for the introduction and stable expression of genes in the nervous system; strategies for promoting selective cell survival or killing of malignant cells in the CNS.