Journal Article

DZNE-2020-06895

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.

Cavaliere, F. (First author)DZNE* ; Fornarelli, A.DZNE* ; Bertan, F.DZNE* ; Russo, R. ; Marsal Cots, A.DZNE* ; Morrone, L. A. ; Adornetto, A. ; Corasaniti, M. T. ; Bano, D.DZNE* ; Bagetta, G. ; Nicotera, P. (Last author)DZNE*

2019
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-019-40887-x

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.

Keyword(s): Affective Disorders, Psychotic: drug therapy (MeSH) ; Affective Disorders, Psychotic: pathology (MeSH) ; Animals (MeSH) ; Antidepressive Agents, Tricyclic: adverse effects (MeSH) ; Antidepressive Agents, Tricyclic: pharmacology (MeSH) ; Autophagy: drug effects (MeSH) ; Caenorhabditis elegans: drug effects (MeSH) ; Clomipramine: adverse effects (MeSH) ; Clomipramine: pharmacology (MeSH) ; Disease Models, Animal (MeSH) ; Liver: drug effects (MeSH) ; Liver: metabolism (MeSH) ; Mice (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: metabolism (MeSH) ; Norepinephrine: metabolism (MeSH) ; Serotonin: metabolism (MeSH) ; Signal Transduction: drug effects (MeSH)

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Contributing Institute(s):

1. Aging and Neurodegeneration (AG Bano)
2. Synaptic Connectivity and Neurodegeneration (AG Nicotera)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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