LIGHT AND ELECTRON-MICROSCOPIC DISTRIBUTION OF THE AMPA RECEPTOR SUBUNIT, GLUR2, IN THE SPINAL-CORD OF CONTROL AND G86R MUTANT SUPEROXIDE-DISMUTASE TRANSGENIC MICE

Excitotoxicity has been hypothesized to contribute to amyotrophic late ral sclerosis (ALS) neurodegeneration. The similar pattern of vulnerab ility in the spinal cord of mutant superoxide dismutase (SOD-1) transg enic mice and mice treated with excitotoxins supports a role for excit otoxicity in the mechanism of degeneration. The distribution of the lp ha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) class of glutamate receptors (GluRs) with different calcium permeabilities has been proposed as an explanation for this differential vulnerability. G luR2 appears to be the dominant determinant of calcium permeability fo r AMPA receptors; thus, it is critical for their contribution to excit otoxic mechanisms. In this study, we investigate the distribution of G luR2 immunoreactivity in the spinal cord of control and SOD-1 transgen ic mice. GluR2 immunoreactivity is present equally within vulnerable n eurons (i.e., motor neurons and calretinin-immunoreactive neurons) as well as nonvulnerable neurons (i.e., calbindin-immunoreactive neurons and dorsal horn neurons). In addition, postembedding immunoelectron mi croscopy reveals that GluR2 is present in synapses of dorsal and ventr al horn neurons and that the percentage of labeled synapses and number s of immunogold particles per synapse do not vary between these spinal cord regions. Comparing control mice with SOD-1 transgenic mice, at b oth the light and the electron microscopic levels, the distribution an d intensity of GluR2-immunoreactivity do not appear to be altered. The se results suggest that the cellular and synaptic distribution of GluR 2 is not a determinant of the selective vulnerability observed in SOD- I transgenic mice or in ALS patients. (C) 1998 Wiley-Liss, Inc.