title: Requirement of AMPK activation for neuronal metabolic-enhancing effects of antidepressant paroxetine.
abstract: 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.
authors.affiliation: aDepartment of Psychiatry, Institute of Behavioral Science in Medicine bBrain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Jeong
authors.forename: Minsun
authors.initials: M
authors.lastname: Park
authors.forename: Jeong Seon
authors.initials: JS
authors.lastname: Yoon
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Kim
authors.forename: Su Kyoung
authors.initials: SK
authors.lastname: Lee
authors.forename: Eun
authors.initials: E
authors.lastname: Lee
authors.forename: Kee
authors.initials: K
authors.lastname: Namkoong
authors.forename: Eosu
authors.initials: E
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000928:Antidepressive Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D001678:Organelle Biogenesis; D017374:Paroxetine / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate; D000928:Antidepressive Agents; D005947:Glucose; D017374:Paroxetine; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; C486497:PPARGC1A protein, human