Tryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disorders.

Tryptamine derivatives are a family of biogenic amines that have been suggested to be modulators of brain function at physiological concentrations. However, pharmacological concentrations of these amines display amphetamine-like properties, and they seem to play a role in brain disorders. Amphetamines induce autophagy in nerve cells, and this type of cell death has also been involved in neurodegenerative diseases. In the present work, we clearly demonstrate for the very first time that high concentrations of tryptamine (0.1-1 mM) induce autophagy in HT22 and SK-N-SH nerve cell lines and in primary cultures of astrocytes, glial cells being less sensitive than neurons. Ultrastructural cell morphology shows all of the typical hallmarks of autophagy. There is no nuclear chromatin condensation, endoplasmic reticulum and mitochondria are swollen, and a great number of double-membraned autophagosomes and residual bodies can be shown in the cytoplasm. Autophagosomes and residual bodies contain mitochondria, membranes, and vesicles and remain unabridged until the cell membrane is disrupted and the cell dies. The same results have been found when cells were incubated with high concentrations of 5-methoxytryptamine (0.1-1 mM). Our results establish a possible link between the role of tryptamine derivatives in brain disorders and the presence of autophagic cell death in these kinds of disorders. (c) 2006 Wiley-Liss, Inc.