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Requirement of AMPK activation for neuronal metabolic-enhancing effects of antidepressant paroxetine

 Jihyeon Jeong  ;  Minsun Park  ;  Jeong Seon Yoon  ;  Hyunjeong Kim  ;  Su Kyoung Lee  ;  Eun Lee  ;  Kee Namkoong  ;  Eosu Kim 
 NEUROREPORT, Vol.26(7) : 424-428, 2015 
Journal Title
Issue Date
AMP-Activated Protein Kinases/antagonists & inhibitors ; AMP-Activated Protein Kinases/metabolism* ; Adenosine Triphosphate/metabolism ; Antidepressive Agents/pharmacology* ; Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Energy Metabolism/drug effects ; Glucose/metabolism ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Neurons/drug effects* ; Neurons/metabolism* ; Organelle Biogenesis ; Paroxetine/pharmacology* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Serotonin Uptake Inhibitors/pharmacology* ; Transcription Factors/metabolism
AMP-activated protein kinase ; antidepressant ; energy metabolism ; mitochondria ; paroxetine
Reduced glucose metabolism has been implicated as a pathophysiology of depressive disorder. Normalization of such impaired neurometabolism has been related to the therapeutic actions of antidepressant medication. However, the molecular mechanism underlying the neurometabolic actions of antidepressants has not been fully understood. Given that AMP-activated protein kinase (AMPK) is a master switch for energy homeostasis, we aimed to determine whether selective serotonin reuptake inhibitor paroxetine enhances energy metabolism by activating AMPK in neuroblastoma cells. We found that paroxetine dose dependently increased mitochondrial biogenesis, which involves the AMPK-peroxisome proliferator-activated receptor-γ coactivator-1α pathway. In addition, paroxetine-induced AMPK activation increases glucose uptake and ATP production. These neurometabolic effects of paroxetine were suppressed by cotreatment with compound C (CC), an AMPK inhibitor. These findings suggest a possibility that modulation of the AMPK pathway might be a previously unrecognized mechanism underlying the neurometabolic action of antidepressants. Further study is warranted to examine the region-specific and time-specific effects of AMPK modulation by antidepressants on mood-related behaviors.
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1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Namkoong, Kee(남궁기) ORCID logo https://orcid.org/0000-0003-1400-8057
Lee, Eun(이은) ORCID logo https://orcid.org/0000-0002-7462-0144
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