The toxin kainic acid: a study of avian nerve and glial cell response utilizing tritiated kainic acid and electron microscopic autoradiography

Three questions are asked regarding the toxin kainic acid (KA). Does it destroy specific glial cells as well as neurons? Does KA gain access to the cytoplasm in intact cells and to which organelles does it bind? Intracerebral injections of tritiated KA into the pigeon (Columba livia) paleostriatal complex (basal ganglia) coupled with electron microscopic autoradiography revealed the following major points. Kainic acid destroyes oligodendrocytes, with pathophysiology apparent by 30 min after challenge with KA leading to cell destruction by 4 h. The response of astrocytes at the longest observation period (4 h) involves swelling of perivascular endfeet and processes in the neuropil. Reactive microglial-like cells show an accumulation of label in their cytoplasm, but no apparent morphological changes. The label appears in the cytoplasm of intact cells, both glia and neurons early after challenge with the toxin. Label is associated (bound) with mitochondria at an incidence significantly above chance at 30 min, 2 and 4 h after challenge with KA. Two hours after exposure to KA is the critical period where metabolic, physiological and morphological changes occur that lead to cell death. Cell destruction may be a consequence of KA-induced energy depletion. Kainate may interfere with adequate energy production by uncoupling glycolysis and the Krebs cycle in the mitochondria.