title: HFS-Triggered AMPK Activation Phosphorylates GSK3β and Induces E-LTP in Rat Hippocampus In Vivo.
abstract: The AMP-activated protein kinase (AMPK) is a sensor of cellular energy and nutrient status, with substantial amount of cross talk with other signaling pathways, including its phosphorylation by Akt, PKA, and GSK3β.
  
  
  
  Various signaling pathways and energy-consuming transport of glutamate receptors subunits are required in synaptic plasticity. However, it is unknown which energy sensors integrate the signaling pathways in these processes. In this article, we elucidated the role of AMPK activation and GSK3β phosphorylation after HFS during the inducement of early-phase long-term potentiation (E-LTP).
  
  
  
  Synaptic LTP in vivo was induced by high-frequency stimulation (HFS at 200 Hz at a 5-s interval). In addition, phosphorylation of AMPK and glycogen synthase kinase 3β (GSK3β) were measured using Western blotting. The amount of hippocampal AMP, ADP and ATP was measured by HPLC.
  
  
  
  We showed that the phosphorylation of AMPK and GSK3β was significantly increased by HFS in vivo. HFS-induced AMPK activation occurred via increased (AMP + ADP)/ATP ratio and activation of Ca(2+) /calmodulin-dependent kinase kinase beta (CaMKKβ). Pharmacological inhibition of AMPK by compound C (CC) prevented HFS-induced inhibitory phosphorylation of GSK3β and the induction of LTP in dentate gyrus (DG) area in vivo.
  
  
  
  Our findings reveal that HFS-triggered AMPK activation phosphorylates GSK3β and induces E-LTP in vivo.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dan-Fang
authors.initials: DF
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zu-Cheng
authors.initials: ZC
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin-Lei
authors.initials: XL
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.
authors.forename: You
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.|The Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.|The Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China.|Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation (HUST), Wuhan, China.|The Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Long
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018891:Dentate Gyrus / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods*; D004789:Enzyme Activation / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000227:Adenine Nucleotides; D000071679:Glycogen Synthase Kinase 3 beta; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; E-LTP; Glycogen synthase kinase 3β; High-frequency stimulation