The antipsychotic agent clozapine induces autophagy via the AMPK-ULK1-Beclin1 signaling pathway in the rat frontal cortex

Progress in Neuro-psychopharmacology & Biological Psychiatry
Se Hyun KimYong Sik Kim

Abstract

Clozapine, a representative atypical antipsychotic, has superior efficacy compared to other antipsychotic agents and is used for the treatment of severe psychotic disorders. Therefore, studies on its mechanisms of action are important for understanding the mechanisms of therapeutic approaches to psychosis. Adenosine monophosphate-activated protein kinase (AMPK) is a serine-threonine kinase that plays a major role in maintaining metabolic homeostasis. Unc-51-like kinase 1 (ULK1) and Beclin1 are downstream substrates of AMPK and activate the autophagic process. In this study, we examined the effects of clozapine on the AMPK-ULK1-Beclin1 signaling pathway and autophagy in the frontal cortex of the rat. Clozapine (10mg/kg) administration increased the immunoreactivity of p-Thr172-AMPKα in the rat frontal cortex at 1, 2, and 4h after injection, as we previously reported. The immunoreactivity of p-Ser317-ULK1 and p-Ser93-Beclin1 was also increased at 2 and 4h after clozapine injection. At the same time, the immunoreactivity of LC3-II and the Atg5-Atg12 conjugate, which indicate activation of autophagy, was increased. Transmission electron microscopy clearly showed an increase in autophagosome number in the rat frontal cortex at 2h af...Continue Reading

Citations

Aug 1, 2018·International Journal of Molecular Sciences·Larisa RyskalinFrancesco Fornai
Oct 1, 2019·Current Opinion in Allergy and Clinical Immunology·Mark J PonsfordStephen Jolles
Nov 26, 2020·Cancers·Valdenizia R SilvaDaniel P Bezerra
Mar 8, 2021·Experimental Neurology·Xiaoyu WangJianmin Zhang
Apr 23, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jun Hyoung JeonMin Jae Lee
May 22, 2021·Pharmacological Reviews·Samantha Christine SernoskieJack Paul Uetrecht
Jun 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Simone PatergnaniPaolo Pinton
Jul 24, 2021·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Seong Hoon Jeong, Yong Sik Kim

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