TY  - JOUR
AU  - Cavaliere, Federica
AU  - Fornarelli, Alessandra
AU  - Bertan, Fabio
AU  - Russo, Rossella
AU  - Marsal Cots, Anais
AU  - Morrone, Luigi Antonio
AU  - Adornetto, Annagrazia
AU  - Corasaniti, Maria Tiziana
AU  - Bano, Daniele
AU  - Bagetta, Giacinto
AU  - Nicotera, Pierluigi
TI  - The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.
JO  - Scientific reports
VL  - 9
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2020-06895
SP  - 4881
PY  - 2019
AB  - 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.
KW  - Affective Disorders, Psychotic: drug therapy
KW  - Affective Disorders, Psychotic: pathology
KW  - Animals
KW  - Antidepressive Agents, Tricyclic: adverse effects
KW  - Antidepressive Agents, Tricyclic: pharmacology
KW  - Autophagy: drug effects
KW  - Caenorhabditis elegans: drug effects
KW  - Clomipramine: adverse effects
KW  - Clomipramine: pharmacology
KW  - Disease Models, Animal
KW  - Liver: drug effects
KW  - Liver: metabolism
KW  - Mice
KW  - Neurons: drug effects
KW  - Neurons: metabolism
KW  - Norepinephrine: metabolism
KW  - Serotonin: metabolism
KW  - Signal Transduction: drug effects
LB  - PUB:(DE-HGF)16
C6  - pmid:30890728
C2  - pmc:PMC6424961
DO  - DOI:10.1038/s41598-019-40887-x
UR  - https://pub.dzne.de/record/140573
ER  -