title: Pilocarpine-induced epilepsy is associated with actin cytoskeleton reorganization in the mossy fiber-CA3 synapses.
abstract: Dramatic structural changes have been demonstrated in the mossy fiber-CA3 synapses in the post status epilepticus (SE) animals, suggesting a potential reorganization of filamentous actin (F-actin) network occurring in the hippocampus. However, until now the long-term effects of SE on the synaptic F-actin have still not been reported. In this study, phalloidin labeling combined with confocal microscopy and protein analyses were adopted to investigate the effects of pilocarpine treatment on the F-actin in the C57BL/6 mice. As compared to the controls, there was ∼ 43% reduction in F-actin density in the post SE mice. Quantitative analysis showed that the labeling density and the puncta number were significantly decreased after pilocarpine treatment (p<0.01, n=5 mice per group, Student's t-test). The puncta of F-actin in the post SE group tended to be highly clustered, while those in the controls were generally distributed evenly. The mean puncta size of F-actin puncta was 0.73±0.19μm(2) (n=1102 puncta from 5 SE mice) in the experimental group, significantly larger than that in the controls (0.51±0.10μm(2), n=1983 puncta from 5 aged-matched control mice, p<0.01, Student's t-test). These observations were well consistent with the alterations of postsynaptic densities in the same region, revealed by immunostaining of PSD95, suggesting the reorganization of F-actin occurred mainly postsynaptically. Our results are indicative of important cytoskeletal changes in the mossy fiber-CA3 synapses after pilocarpine treatment, which may contribute to the excessive excitatory output in the hippocampal trisynaptic circuit.
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin Province 130021, PR China; Pediatric Neurology, First Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Tian-Qing
authors.initials: TQ
authors.lastname: Xiong
authors.affiliation: Laboratory Teaching Center of Basic Medicine, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Bai-Hong
authors.initials: BH
authors.lastname: Tan
authors.affiliation: Nursing College, Beihua University, Jilin, Jilin Province 132013, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Shu-Lei
authors.initials: SL
authors.lastname: Li
authors.affiliation: Pediatric Neurology, First Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Yang
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin Province 130021, PR China. Electronic address: liyanchao@jlu.edu.cn.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D016704:Synapsins / Q000378:metabolism
chemical_list: D000199:Actins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D018721:Muscarinic Agonists; D016704:Synapsins; D010862:Pilocarpine; D051528:Guanylate Kinases
keywords: Filamentous actin; Mossy fiber; Pilocarpine; Status epilepticus