title: Age- and disease-related neuroplasticity of chemically identified neuronal circuits: a tribute to Professor Erminio Costa.
abstract: The following review highlights a small portion of the research ongoing in my laboratory at the Fidia Georgetown Institute of Neuroscience (FGIN) during the years 1989-1994. Specifically, this work focused on the selective vulnerability of neurons in Alzheimer's disease. At the time, it was known that α-amino-3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptors were composed of one or more subunits (GluR1-4). Furthermore, the presence of the GluR2 subunit was known to substantially reduce Ca2+ through AMPA receptors in response to ligand binding. This finding led us to hypothesize that the presence or absence of the GluR2 subunit in the AMPA receptor may have a profound influence on the ability of the cell to gate extracellular Ca2+ and maintain intracellular calcium homeostasis. Furthermore, in Alzheimer's disease we hypothesized that cells at risk for developing AD neuropathology will express certain combinations of glutamate receptor subunits that form channels with increased permeability to Ca2+. In turn, these cells may become more vulnerable to the pathologic consequences of increased intracellular Ca2+ and destabilized intracellular Ca2+ homeostasis. To test this hypothesis we employed anatomical techniques and examined post mortem materials from patients with AD. The results of these studies are summarized in this review. Notably, this review also highlights the valuable collaborations established during my five years at FGIN and pays tribute to the intellectually rich and supportive environment provided by Dr. Costa and colleagues.
authors.affiliation: National Institute of Mental Health, National Institutes of Health, Neuroscience Building, Room 6138, 6001 Executive Blvd, MSC 9606, Bethesda, MD 20892-9605, United States. armstrda@mail.nih.gov
authors.forename: David
authors.initials: D
authors.lastname: Armstrong
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000846:Anniversaries and Special Events; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity; D018091:Receptors, AMPA / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid