title: Activation of ERK1/2-CREB pathway during potentiating synaptic transmission of (-)clausenamide in rat dentate gyrus.
abstract: To investigate the signal mechanism of (-)clausenamide ((-)-3-hydroxy-5-(hydroxy-phenyl-methyl)-1-methyl-4-phenyl-pyrrolidin-2-one, 1) and for understanding its effect on synaptic transmission, electrophysiological recording was done for basal synaptic transmission determination. Western blot analysis was employed to examine the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP responsive element-binding protein (CREB). Immunohistochemistry and tissue in situ hybridization were applied to detect the expression of Zif268. The results showed that (-)clausenamide (1) increased the population spike of hippocampal dentate gyrus. The phosphorylation of ERK1/2 in hippocampus and cortex was increased and reached the maximum at 5 min and 30 min, respectively. (-)Clausenamide (1) promoted the phosphorylation of CREB, the downstream protein of ERK1/2. The expression of Zif268 protein and mRNA increased in both hippocampal dentate gyrus and cortex. Therefore, (-)clausenamide (1) activated the ERK1/2-CREB pathway, which may provide an explanation for its effect on potentiating synaptic transmission and improving learning and memory.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.forename: Fei
authors.initials: F
authors.lastname: Niu
authors.forename: Na
authors.initials: N
authors.lastname: Ning
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Duan
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Chu
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
authors.forename: Jun-Tian
authors.initials: JT
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects*; D051766:Early Growth Response Protein 1 / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015394:Molecular Structure; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D007769:Lactams; D017705:Lignans; C053048:clausenamide; D048052:Mitogen-Activated Protein Kinase 3