Research Description

The primary research focus of the laboratory began with the regulation of neuronal plasticity (axonal regeneration, sprouting and synaptogenesis) during normal development and following injury to the developing or mature brain. Discoveries led to more recent emphasis on the role of geometry in CNS regeneration and the role of apoE in Alzheimer's disease. A 5-year NIH grant to study apoE is now in progress. In addition, a 4-year NIH grant is underway for studies on NGF and axonal regeneration.

Previous work from this laboratory demonstrated that: 1) Nerve Growth Factor may be implicated in at least one form of axonal sprouting that occurs following focal brain injury in the rat (refs), 2) white matter in the mature brain inhibits or promotes axonal regeneration in tissue culture depending on geometry (refs), 3) infusion of NGF into the rat brain results in the hyperinnervation of extracerebral blood vessels and the rearrangement of some axonal projections (refs), 4) the decline in neuronal plasticity that occurs in the aged brain is primarily due to loss of growth support by the brain environment (refs), and 5) Alzheimer's brain tissue shows an elevation of NGF levels (refs).

The demonstration that NGF is elevated in Alzheimer's disease led to a consideration of factors that may directly cause neuronal degeneration (thereby leading to secondary accumulation of target growth factor). This research line has since led to discoveries of isoform-specific neurotoxicity of apoE and a recent hypothesis that proteolytic fragments of this molecule may contribute to the major pathologies of Alzheimer's disease (plaques and tangles)(refs).