Composition of ibotenic acid-induced calcifications in rat substantia nigra

Abstract

Agonists of the excitatory neurotransmitter glutamate have neurotoxic properties and are, therefore, frequently used to place locally circumscript brain lesions. In certain vulnerable brain areas, especially the substantia nigra and globus pallidus, the ensuing neurodegeneration is accompanied by the formation of calcium deposits. In the present study, we investigated the structure and chemical composition of calcium deposits formed in rat substantia nigra upon local application of ibotenic acid. Using scanning and transmission electron microscopy in combination with X-ray analysis and analysis of the electron diffraction patterns, we demonstrate that the inorganic components of the calcifications consist of calcium and phosphate. The calcium phosphate is deposited in a polycrystalline manner in degenerating neurons and in a matrix surrounding the degenerated complexes. New matrix is continuously added around the enlarging calcium deposits. Content of inorganic material is always higher in the center of the deposits than in the margin, but in every case the diffraction pattern reveals that the calcium phosphates are present in the form of hydroxyapatite. Thus, organic and inorganic components of the calcifications are subject to a continuous process of growth and maturation. The ibotenic acid-induced calcium deposits in rat substantia nigra provide a reliable model system to study the pathogenesis of non-arteriosclerotic calcifications.