title: Tryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disorders.
abstract: 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.
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, C/Julian Claveria, 33006 Oviedo, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Herrera
authors.forename: Vanesa
authors.initials: V
authors.lastname: Martin
authors.forename: Pilar
authors.initials: P
authors.lastname: Carrera
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Santos
authors.forename: Jezabel
authors.initials: J
authors.lastname: Rodriguez-Blanco
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Isaac
authors.initials: I
authors.lastname: Antolín
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D022083:Cytoplasmic Structures / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006801:Humans; D046529:Microscopy, Electron, Transmission; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000633:toxicity; D018490:Serotonin Agents / Q000633:toxicity; D014363:Tryptamines / Q000633:toxicity*
chemical_list: D018490:Serotonin Agents; D014363:Tryptamines; D012701:Serotonin; C030820:tryptamine