GluR2 expressed by glial fibrillary acidic protein promoter decreases the number of neurons

Abstract

The alpha - amino-3 - hydroxyl - 5 -methyl - 4-isoxazolepropionic acid (AMPA) type ionotropic glutamate receptors participate in fast neuronal transmission. GluR2, a subunit of AMPA receptors, is the determinant of Ca 2+-permeability and surface expression of the receptors. To elucidate the role of AMPA receptors in the cells expressing glial fibrillary acidic protein (GFAP), we constructed mice expressing rat GluR2 cDNA under the control of a human GFAP promoter. The mice expressed approximately two folds increase of GluR2 in primary culture of astrocytes. Colocalization of GluR2 and GFAP was observed in Bergmann glial cells, which normally expressed AMPA receptors lacking GluR2. The diameter of glial fibers was significantly reduced and the leading edge of the processes was thinning or retracted in primary cultured BG cells. Interestingly, the transgenic mice had smaller brains compared with wild type mice. We found a 32% decrease in the number of cerebellar granule cells and a 31% decreases in cerebral cortical neurons. These results indicate that the increased expression of GluR2 in GFAP-positive cells alters neuron-glial interaction and leads to reduction in the number of neurons in adult mice.