title: MPP+inhibits mGluR1/5-mediated long-term depression in mouse hippocampus by calpain activation.
abstract: Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP+incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses. Our further findings indicated that, this blockage was reversed by pre-application of calpain inhibitor III, but not by cathepsin inhibitors. Biochemical analysis showed that MPP+treatment stimulated calpain activation, displayed by spectrin breakdown. Interestingly, the level and activity of protein tyrosine phosphatase 1B (PTP1B) were reduced after MPP+incubation and the decrease of PTP1B was prohibited by calpain inhibitor III. In addition, PTP1B inhibitor also blocked DHPG-induced LTD, mimicking the effect of MPP+. In summary, our data implicated that MPP+activated calpain-dependent PTP1B degradation, which subsequently impaired hippocampal LTD. This novel effect of MPP+might partially explain the impairment of memory processing in the pathogenesis of PD.
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Junyao
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Wu
authors.affiliation: Jitang College of North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Yuefa
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China. Electronic address: wangjing2161@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China. Electronic address: guoqizhu@gmail.com.
authors.forename: Guoqi
authors.initials: G
authors.lastname: Zhu
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; D002154:Calpain; D015655:1-Methyl-4-phenylpyridinium; C010117:3,4-dihydroxyphenylglycol
keywords: Calpain; DHPG; Hippocampus; Long-term depression; MPP(+)