Basal ganglia calcification induced by excitotoxicity: an experimental model characterised by electron microscopy and X-ray microanalysis

Abstract

Activation of glutamate receptors induces an excitotoxic neurodegenerative process characterised in some brain areas by the formation of calcium precipitates. To examine the pathogenesis of basal ganglia calcification (BGC), an improved procedure of X-ray microanalysis was used to study experimental excitotoxic calcification in the rat. Three weeks after injection of ibotenic acid (IBO) in the rat basal forebrain, calcified inclusions within hypertrophied astrocytes were characterised. They appeared to form part of a filamentous structure localised in the cytoplasm in association with normal mitochondria and other organelles. Larger inclusions were surrounded by reactive microglia. The main inorganic components in these deposits were Ca and P, frequently accompanied by S, Al, Si and K. The shape and Ca/P molar ratio of the large deposits (> 10 μm) indicate that they may be biological apatites. Aluminosilicates were detected as small deposits (< 4 μm) free of other mineral constituents. To our knowledge this is the first report showing that IBO lesion induces brain accumulation of aluminosilicates similar to that described in Alzheimer’s or Fahr’s patients. Our data indicate that precipitation of Ca and Al may reduce their IBO-induced increased concentration. In conclusion, the experimental model and the improved efficiency of X-ray analysis described may help us to understand the pathogenesis of BGC.