A key focus of our laboratory is to examine molecular mechanisms of degeneration of brain neurons. Many of our studies are carried out in dissociated nerve cell cultures, a system that has the advantage over more complex systems of allowing precise control of the neuronal microenvironment and thereby facilitating determination of conditions that modulate neuronal behaviors (such as calcium accumulation or excitability) or survival.
A current focus follows from the observation that neuronal death in certain degenerative diseases (including Alzheimer’s disease and amyotrophic lateral sclerosis) is selective; certain populations of neurons die while others seem unaffected by the disease. What differentiates the vulnerable neurons from the others? Several lines of evidence have led us to suggest that vulnerable neurons might differ from other neurons in their sensitivity to damage produced by activation of AMPA/kainate subtypes of glutamate receptors, in part because of expression of calcium permeable AMPA/kainate channels.
Specific current areas of focus include:
• Roles of calcium and zinc ions in excitotoxic injury: routes of entry, intracellular regulation, and intracellular effects.
• Ca2+ permeable AMPA/kainate channels: Their expression, function and roles in neural signaling and in selective neurodegeneration.
• Mitochondrial dysfunction and free radical generation in neuronal injury.
Cellular mechanisms of nerve cell loss in Alzheimer’s disease, Amyotrophic
• Lateral Sclerosis, stroke and epilepsy.
• Trophic factors and interneuronal signaling in neuronal survival and growth:
in vitro models.