8 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 - Jan 1 2017

Fingerprint

Sertraline
Paroxetine
Astrocytes
Antidepressive Agents
Apoptosis
Calcium
Serotonin Uptake Inhibitors
Neurodegenerative Diseases
Dementia
Neurons
Serotonin Antagonists
Tricyclic Antidepressive Agents
Caspase 3
Oxides
Serotonin
Cell Survival
Central Nervous System
Depression
Cell Line

Keywords

  • Antidepressants
  • Astrocyte apoptosis
  • Calcium overload
  • Mitochondrial damage

ASJC Scopus subject areas

  • Oncology

Cite this

Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes. / Then, Chee Kin; Liu, Kao Hui; Liao, Ming Hsuan; Chung, Kuo Hsuan; Wang, Jia Yi; Shen, Shing Chuan.

In: Oncotarget, Vol. 8, No. 70, 01.01.2017, p. 115490-115502.

Research output: Contribution to journalArticle

@article{40da0db65a9047b99bbc22ce8407a25f,
title = "Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes",
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.",
keywords = "Antidepressants, Astrocyte apoptosis, Calcium overload, Mitochondrial damage",
author = "Then, {Chee Kin} and Liu, {Kao Hui} and Liao, {Ming Hsuan} and Chung, {Kuo Hsuan} and Wang, {Jia Yi} and Shen, {Shing Chuan}",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.23302",
language = "English",
volume = "8",
pages = "115490--115502",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "70",

}

TY - JOUR

T1 - Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes

AU - Then, Chee Kin

AU - Liu, Kao Hui

AU - Liao, Ming Hsuan

AU - Chung, Kuo Hsuan

AU - Wang, Jia Yi

AU - Shen, Shing Chuan

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Antidepressants

KW - Astrocyte apoptosis

KW - Calcium overload

KW - Mitochondrial damage

UR - http://www.scopus.com/inward/record.url?scp=85039708476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039708476&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.23302

DO - 10.18632/oncotarget.23302

M3 - Article

AN - SCOPUS:85039708476

VL - 8

SP - 115490

EP - 115502

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 70

ER -