| Anatomical and Functional Plasticity in the Intact and Injured Adult CNS |
This laboratory studies anatomical, electrophysiological and functional plasticity in the intact and injured adult central nervous system. We focus in particular on the functional role of growth factors in modulating plasticity. Models studied in the lab include: 1) mechanisms of learning and memory in the intact adult brain, 2) plasticity and cell degeneration in models of aging and Alzheimer's disease, and 3) axonal plasticity and regeneration after spinal cord injury. In the intact brain, we examine changes in neuronal structure and function that occur during normal learning, and the role of neurotrophic factors in modulating these changes. In models of basal forebrain and cortical degeneration in rodents and primates, the ability of neurotrophic factors delivered by gene therapy to modulate cellular plasticity and survival are examined;these studies are relevant to the understanding of aging and neuronal loss in Alzheimer's disease. In rodent and primate models of spinal cord injury, we examine the influences of growth factors and extracellular matrix molecules in modulating axonal responses to injury and the ability of these substances to promote axonal regeneration.
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Conner JM, Chiba AA, Tuszynski MH. The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuron, 2005, 46:173-9.
Tuszynski MH et al. A phase I clinical trial of nerve growth factor gene therapy for Alzheimer’s disease. Nature Med, 2005, 11:551-5.
Yang H, Lu P, McKay HM, Bernot T, Keirstead H, Steward O, Gage FH, Edgerton ER, Tuszynski MH. Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury.
Journal of Neuroscience 2006; 26:2157-66
Taylor L, Jones L, Tuszynski MH, Blesch A. Neurotrophin-3 gradients established by lentiviral gene delivery promote short-distance axonal bridging beyond cellular grafts in the injured spinal cord.
Journal of Neuroscience 2006; 26:9713-9721.
Lu P, Yang H, Culbertson M, Graham L, Roskams JA, Tuszynski MH. Olfactory ensheathing cells do not exhibit unique migratory or axonal growth-promoting properties after spinal cordiInjury.
Journal of Neuroscience 2006: 26:11120-11130.
Tuszynski MH. Challenges to the report of nogo antibody effects in primates. Nature Med 2006; 12:1231-1232.
Ramanathan D, Conner JM, Tuszynski, MH. A novel form of motor cortical plasticity that correlates with recovery of function after brain injury. Proc Natl Acad Sci, 2006;10330:11370-11375.
Blesch A, Tuszynski MH. Transient growth factor delivery sustains regenerated axons after spinal cord injury.
Journal of Neuroscience, 2007; 27:10535-10545.
Tuszynski MH. Rebuilding the brain: resurgence of fetal grafting. Nature Neurosci., News & Views. 2007; 10:1-2.
Löw K, Culbertson M, Bradke F, Tessier-Lavigne M, Tuszynski MH. Netrin-1 is a novel myelin-associated inhibitor to axon growth.
Journal of Neuroscience 2008, in press.
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