title: Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus.
abstract: This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis.
authors: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Chun-Yao
authors: CY
authors: Lee
authors: Thomas
authors: T
authors: Jaw
authors: Huan-Chin
authors: HC
authors: Tseng
authors: I-Chun
authors: IC
authors: Chen
authors: Horng-Huei
authors: HH
authors: Liou
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D018891:Dentate Gyrus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000517:prevention & control; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D036341:Intercellular Signaling Peptides and Proteins; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018721:Muscarinic Agonists / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013226:Status Epilepticus / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000924:Anticholesteremic Agents; D036341:Intercellular Signaling Peptides and Proteins; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D010862:Pilocarpine; D008148:Lovastatin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3