Pilocarpine-Induced Status Epilepticus Is Associated with Changes in the Actin-Modulating Protein Synaptopodin and Alterations in Long-Term Potentiation in the Mouse Hippocampus.
Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity.
Department of Neurology, The Chaim Sheba Medical Center, Tel HaShomer, Israel; Institute of Anatomy II, Faculty of Medicine, Heinrich-Heine University, Düsseldorf, Germany; Institute of Clinical Neuroanatomy, Neuroscience Center Frankfurt, Goethe University, Frankfurt, Germany.
Maximilian
M
Lenz
Department of Neurology, The Chaim Sheba Medical Center, Tel HaShomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Marina
M
Ben Shimon
Institute of Clinical Neuroanatomy, Neuroscience Center Frankfurt, Goethe University, Frankfurt, Germany.
Thomas
T
Deller
Institute of Anatomy II, Faculty of Medicine, Heinrich-Heine University, Düsseldorf, Germany.
Andreas
0000-0002-2646-3770
A
Vlachos
Department of Neurology, The Chaim Sheba Medical Center, Tel HaShomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel HaShomer, Israel; Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Nicola
0000-0001-9632-3338
N
Maggio
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010862:Pilocarpine / Q000633:toxicity*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology
D000199:Actins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; C503968:Synpo protein, mouse; C028514:actin-modulating proteins; D010862:Pilocarpine