Neurobiology of Brain Disorders

Affiliation: Professor of Neurology, Department of Neurology, University of Pittsburgh, Pennsylvania, U.S.A Over the past year, Dr. Zigmond and his research team have continued their studies of cellular and animal models to examine Parkinson's disease (PD), which they believe is a multi-factorial disorder. A major focus of the lab is the role of intracellular signaling cascades in determining the viability of dopamine (DA) neurons. They hypothesize, for example, that trophic factors such as GDNF and oxidative stress can both stimulate intracellular survival cascades, including those involving MAP kinases. They further believe that endogenous trophic factor expression can be enhanced by exercise which in turn can be neuroprotective. And they have evidence that protection also can derive from acute exposure to low levels of a neurotoxin, a form of preconditioning. Last year their work included studies of the impact of oxidative stress induced by 6-hydroxydopamine (6-OHDA), a DA analogue that is concentrated in DA cells and rapidly breaks down to form reactive oxygen species. Results from these and other studies suggest that DA neurons react to stress by initiating a set of protective responses. Learning more about these responses may provide insights into new treatment modalities for PD. In the coming year, Dr. Zigmond will continue to focus on understanding the strategies DA neurons use to reduce their vulnerability to intracellular stress. For example, studies are underway to determine if inhibition of trophic actor action or of kinase activation will block neuroprotection seen with exercise or GDNF or increase 6-OHDA toxicity. Some of these studies involve the preparation of molecular biological tools that maintain kinases in a constitutively or dominant negative state and/or localize a kinase to the cytoplasm or the nucleus. In addition, histochemical methods are being developed to quantify kinase levels in different cellular compartments of identified cells. Joseph T. Coyle, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA

1. An Introduction: A Clinical Neuroscientist and Disorders of the Brain Section I: Developmental Disorders2. Introduction3. Developmental Disabilities and Metabolic Disorders4. Attention-Deficit/Hyperactivity Disorder5. Down Syndrome: A Model for Chromosome Abnormalities6. Autism Spectrum Disorder7. Rett Syndrome: From the Involved Genes to Treatment8. Fragile X-associated DisordersSection II: Diseases of the Peripheral Nervous System9. Introduction10. Myasthenia Gravis 11. Muscular Dystrophy12. Peripheral Neuropathies and Guillain-Barré Syndrome13. Diabetes and Its ConsequencesSection III: Diseases of the Central Nervous System and Neurodegeneration14. Introduction15. Spinal Cord Injury16. Traumatic Brain Injury17. Epilepsy18. ALS and Related Motor Neuron Disorders (Including Spastic Paraplegia)19. Parkinsonian Syndromes20. Huntington Disease21. Alzheimer Disease and Other Dementias22. Cerebrovascular Disease23. Prion DiseaseSection IV: Infectious and Immune–mediated Diseases Affecting the Nervous System24. Introduction25. Inflammation in Neurological Disease 26. Inflammation in Psychiatric Disease27. Infectious Diseases of the Nervous System28. AIDS29. Autoimmune Neurological Disorders: Idiopathic and Paraneoplastic30. Multiple SclerosisSection V: Diseases of Higher Function31. Introduction32. Disorders of Higher Cortical Function 33. Disorders of Frontal Lobe Function 34. Stress35. Addictions 36. Sleep Disorders, Narcolepsy, and Restless Leg Syndrome37. Anxiety Disorders and Post-traumatic Stress Disorder38. Obsessive Compulsive Disorder39. The Neurobiology of Schizophrenia 40. Bipolar Disorders41. Pain42. Headache and Migraine43. Depression and SuicideSection VI: Diseases of the Nervous System and Society44. Introduction45. Ethical Issues that Emerge from Research (Basic)46. Burden of Neurological Disease47. Stress, Race, and Health Disparities