title: Microcystin-LR inhibited hippocampal long-term potential via regulation of the glycogen synthase kinase-3β pathway.
abstract: We previously demonstrated that Cyanobacteria-derived microcystin-LR (MCLR) is able to induce cognitive dysfunction, but the mechanism is not understood. Long-term potential (LTP) in hippocampus is regarded as an important cellular mechanism of learning and memory. Here, the aim of this study was to evaluate the role of MCLR in LTP of hippocampal dentate gyrus (DG) by in vivo electrophysiological recording. We found that MCLR could suppress the induction of LTP in rat hippocampus, whereas simultaneous inhibition of glycogen synthase kinase-3β (GSK-3β) by LiCl or SB216763 attenuated the LTP impairments by MCLR. Furthermore, a decrease of the phosphorylated level at Ser9 of GSK-3β was observed by western blotting after intracerebroventricular (ICV) injection of MCLR, indicating GSK-3β was activated by MCLR. In addition, we showed that ICV administration of MCLR slightly stimulated activity of protein phosphatases (PPs) in the brain, which might activate GSK-3β via dephosphorylation of Ser9 site. Taken together, these findings demonstrated that GSK-3β plays a crucial role in regulating MCLR-induced cognitive deficit.
authors.affiliation: College of Fisheries, Huazhong Agriculture University, Wuhan 430070, PR China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.forename: Fankai
authors.initials: F
authors.lastname: Lin
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D009498:Neurotoxins; D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C057862:cyanoginosin LR
keywords: Glycogen synthase kinase-3β; Hippocampus; Long-term potential; Microcystin-LR