Neurotoxic effects of partially oxidized serotonin: tryptamine-4,5-dione

Neurotoxicity of tryptamine-4,5-dione (4,5-DKT), a partially oxidized form of serotonin, was assessed after microinjection into the lateral ventricle, hippocampus, or cingulate cortex of rats followed by Fink-Heimer staining for axon terminal degeneration. Intracerebroventricular injections of 4,5-DKT resulted in terminal degeneration which was most dense in layers I and III of insular cortex, layer I of cingulate cortex, and the molecular layer of the dentate gyrus. Argyrophilic and probably degenerating neurons were most frequently subjacent to the granule cell layer of the dentate gyrus, layers II, III, and IV of entorhinal cortex, and throughout the insula. Injections of 5-20 micrograms of 4,5-DKT directly into the hippocampus indicated that toxicity was dose-dependent. These injections produced axon terminal degeneration and neuronal argyrophilia in sectors CA1 and CA3 and in the dentate gyrus. Argyrophilic neurons were also observed in layers II, III, and IV of ipsi- and contralateral entorhinal cortices. Injections into anterior and posterior cingulate cortices produced degeneration in the caudate and anterior thalamic nuclei, and contralateral cortex. These results indicate that 4,5-DKT is a novel indole neurotoxin which exhibits a striking propensity for medial limbic system structures including some of those affected in dementia of the Alzheimer type.