Neurodegeneration in the developing and mature brain
My current research includes collaborative studies with the Departments of Psychiatry, Neurology and Cold Spring Harbor Laboratories. We have previously shown that during brain development and synaptogenesis there are several mechanisms by which massive neurodegeneration can be induced. Insufficient activation of NMDA glutamate receptors or excessive activation of GABA-A receptors triggers widespread apoptotic neurodegeneration. Ethanol, with both NMDA receptor blocking and GABA-A receptor activating properties, also causes widespread apoptotic neurodegeneration throughout the developing forebrain during synaptogenesis including the cortex, various brain stem nuclei as well as in the cerebellum. This provides an explanation for the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome. Based on our data we were able to characterize strict EM criteria for the progression of apoptotic cell death in the developing CNS. Additionally we are now following the role of various types of anesthetics used in pediatric surgery studying their morphological impact on the fetal and neonatal primate brain. My current research focuses also on the mechanisms and mechanical forces (strain fields) that trigger acute as well as protracted cell death and axonal degeneration in traumatic brain injury conditions and compares patterns of neurodegeneration mechanisms in newborn and adult animals. In collaboration with the Department of Neurology we are studying the ultramicroscopic structure of the Alzheimer-type plaque and the nature and development of neurodegenerative processes in various transgenic animal models. Additionally I am studying the significance of the close relationship of dentate gyrus generated adult stem cell apical processes to the local vascular periphery.