Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes

Chee Kin Then, Kao Hui Liu, Ming Hsuan Liao, Kuo Hsuan Chung, Jia Yi Wang, Shing Chuan Shen

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The impacts of antidepressants on the pathogenesis of dementia remain unclear despite depression and dementia are closely related. Antidepressants have been reported may impair serotonin-regulated adaptive processes, increase neurological side-effects and cytotoxicity. An 'astroglio-centric' perspective of neurodegenerative diseases proposes astrocyte dysfunction is involved in the impairment of proper central nervous system functioning. Thus, defining whether antidepressants are harmful to astrocytes is an intriguing issue. We used an astrocyte cell line, primary cultured astrocytes and neuron cells, to identify the effects of 11 antidepressants which included selective serotonin reuptake inhibitors, a serotonin-norepinephrine reuptake inhibitor, tricyclic antidepressants, a tetracyclic antidepressant, a monoamine oxide inhibitor, and a serotonin antagonist and reuptake inhibitor. We found that treatment with 10 μM sertraline and 20 μM paroxetine significantly reduced cell viability. We further explored the underlying mechanisms and found induction of the [Ca2+]i level in astrocytes. We also revealed that sertraline and paroxetine induced mitochondrial damage, ROS generation, and astrocyte apoptosis with elevation of cleaved-caspase 3 and cleaved-PARP levels. Ultimately, we validated these mechanisms in primary cultured astrocytes and neuron cells and obtained consistent results. These results suggest that sertraline and paroxetine cause astrocyte dysfunction, and this impairment may be involved in the pathogenesis of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)115490-115502
Number of pages13
JournalOncotarget
Volume8
Issue number70
DOIs
Publication statusPublished - 2017

Keywords

  • Antidepressants
  • Astrocyte apoptosis
  • Calcium overload
  • Mitochondrial damage

ASJC Scopus subject areas

  • Oncology

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