Neuroregeneration Laboratories, Program in Neuroscience, Harvard Medical School McLean Hospital and Massachusetts General Hospital

NEURAL SYSTEMS: DYNAMIC MECHANISMS INVOLVED IN CNS REGENERATION AND DEGENERATION

see Neuroregeneration.org

This program focuses on the mechanisms and dynamics of neuronal regeneration (1,3,5-6), degeneration and protection (2,3) with particular emphasis on the neurodegenerative disorders like Parkinson's, Huntington's, and Alzheimer's . Our understanding of regeneration and plasticity of the mammalian nervous system has developed greatly over the last decade, due to basic research in rats following implantation of fetal, cultured or genetically engineered cells into the adult brain . While the adult brain previously was thought of as a non-regenerative system for pathway formation, recent studies show how dissociated primordial neurons implanted into the adult central nervous system can grow to reconnect neuronal pathways and integrate in a molecular and physiological fashion. Thus, anatomical, neurochemical, molecular and behavioral parameters indicate that reconstructive events can take place also in the degenerated adult brain (1-6).

The cellular, physiological and molecular events associated with progressive neuronal death and degeneration in the neurodegenerative diseases are still unknown. We search for causal events involved in maintaining neuronal plasticity and health on a cellular level, by (a); constructing model systems that as closely as possible simulate the regional and cellular degeneration seen in brains with neurodegenerative disease, and (b); testing various factors and conditions that may prevent or reverse degeneration in such models (1, 3-6). These studies combined are likely to yield to a better understanding of regeneration, development and plasticity of the brain both at a cellular and system integration level. In addition, our research may lead to future therapies for neurodegenerative disease.

Key words: Parkinson's, Huntington's, Alzheimer's, Treatments, Neural transplants, Neuroprotection, Gene Therapy, Animal models

Project Sites. Neuroregeneration Lab., Dept. of Neurology and Program of Neuroscience, Harvard Medical School, McLean Hospital/Massachusetts General Hospital (Dr. Ole Isacson). Harvard Medical School, New England Regional Primate Research Center, (Dr. Roger Spealman). Massachusetts General Hospital, Dept. of Radiology, Boston (Dr. Anna-Liisa Brownell). Massachusetts General Hospital, Neurosurgery Research, Boston (Dr. Robert L. Martuza). Massachusetts General Hospital, Neurogenetics Lab., Charlestown (Dr. Xandra O. Breakefield). Neurological Associates, Sarasota Florida  (Dr Jim Schumacher).

Program Director. Dr. Ole Isacson , McLean Hospital, Neuroregeneration Laboratory, 115 Mill Street, Belmont, MA 02178. Contact Person, Dr. Ole Isacson, Director, Telephone: (617) 855-3243, FAX: (617) 855-3284, E-Mail: oisacson@hms.harvard.edu - [Biosketch]

Training Opportunities. Currently there are 5 post-doctoral fellows and 2 graduate students. There is a possibility of openings for other trainees at the pre and post-doctoral level if funds are made available.

Representative Publications.

1. Isacson, O. (1995) On behavioral effects and gene delivery in Parkinson's rat model. Science, 269, 856-857
2. Tatter. S.B., Galpern, W.R. and Isacson, O. (1995) Mechanisms of neurotrophic factor protection against excitotoxic neuronal death. The Neuroscientist 1, 286-297.
3. Isacson, O., Deacon, T.W., Pakzaban, P., Galpern, W.R., Dinsmore, J., and Burns, L.H. (1995)  Transplanted xenogeneic neural cells in neurodegenerative disease models  exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nature Med. 1, 1189-1194.
4. Isacson, O. and Deacon, T. (1997) Neural transplantation studies reveal the brain's capacity for continuous reconstruction.  Trends Neurosci. 20, 477-482.
5. Lin, L., Georgievska, B., Mattsson, A. and Isacson, O. (1999) Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation.  Proc. Natl. Acad. Sci. USA 96, 12108-12113.