1. Academic Validation
  2. The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux

The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux

  • Sci Rep. 2019 Mar 19;9(1):4881. doi: 10.1038/s41598-019-40887-x.
Federica Cavaliere 1 2 Alessandra Fornarelli 1 Fabio Bertan 1 Rossella Russo 2 Anaïs Marsal-Cots 1 Luigi Antonio Morrone 2 Annagrazia Adornetto 2 Maria Tiziana Corasaniti 3 Daniele Bano 1 Giacinto Bagetta 2 Pierluigi Nicotera 4
Affiliations

Affiliations

  • 1 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • 2 Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (Cosenza), Italy.
  • 3 Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
  • 4 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. pierluigi.nicotera@dzne.de.
Abstract

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.

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