Ibotenic acid-induced calcium deposits in rat substantia nigra. Ultrastructure of their time-dependent formation

Abstract

The excitotoxin ibotenic acid (IBO) induces local calcium deposits upon injection into rat substantia nigra. Their formation has been investigated at the ultrastructural level in a time course study from 2 days to 8 weeks survival. Potassium bichromate stain was used to visualize pathological calcium accumulation. Two days after IBO application, reaction product for calcium was observed in mitochondria of degenerating perikarya and dendrites, but not in axons, boutons or glia. Four days after the lesion, calcium stain was found, in addition, in a seemingly free form in a few dendrites, especially those still contacted by intact boutons and not sequestrated by invading glia. Two days later, most of these calcium-accumulating dendrites were separated by astroglia from their synaptic partners. At the border between glia and dendrite a fibrillar matrix was formed which further accumulated calcium. During the following weeks this matrix enlarged stepwise and was infiltrated with calcium, thus giving a picture resembling the annual growth rings of trees. The evolving bodies incorporated smaller deposits in their vicinity, finally representing the large concretions seen at the light microscopic level from the 4th postoperative week onward. Similarities and dissimilarities of these observations with the results from other ultrastructural studies on excitotoxin lesions are detailed. It is suggested that the different outfit of neuronal subpopulations and of glia with ligand-gated and metabotropic glutamate receptors in the single brain region, as well as the local response repertoire of glial cells towards the excitotoxic injury with the subsequent formation of a calcium-accumulating matrix provide the molecular basis for the formation of calcium deposits.