@article{61c1ba2771834692ab06717f7f67d28f,
title = "Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy",
abstract = "The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rodents. The relationship between KA-induced neuronal damage and Golgi complex fragmentation has not been investigated, leaving a major gap in our understanding of the molecular mechanism underlying the development of pathophysiology in epilepsy. We cultured primary rat cortical neurons eitherin ambient condition (control) or treated with a range of KA doses to reveal whether Golgi complex fragmentation impaired neuronal function. The half-life maximal inhibitory concentration (IC50) value of KA was detected to be approximately 5 μM, whereby at these concentrations, KA impaired neuronal viability, which was closely associated with initial Golgi complex fragmentation and subsequent reduction in both the expression and glycosylation patterns of Reelin. These findings implicate that Golgi complex fragmentation and Reelin dysfunction are key contributors to neuronal cell death in the early stage of epilepsy pathophysiology, thereby representing as novel disease biomarkers, as well as potent therapeutic targets for epilepsy.",
keywords = "Glycosylation, Golgi protein, Initiating epilepsy, Kainic acid, Primary rat neuronal cell",
author = "Yuji Kaneko and Robert Sullivan and Travis Dailey and {Vale Diaz}, Fernando and Naoki Tajiri and Borlongan, {Cesar V.}",
note = "Funding Information: The authors declare adherence to the journal{\textquoteright}s policies for upholding the integrity of the scientific record, in particular observance of the guidelines set forth by the Committee on Publication Ethics (COPE), including but not limited to the authors refraining from misrepresenting research results which could damage the trust in the journal, the professionalism of scientific authorship, and ultimately the entire scientific endeavor. Along the lines of maintaining integrity of the research and its presentation, the authors follow the rules of good scientific practice, which include the following: (1) The manuscript has not been submitted to more than one journal for simultaneous consideration (2) the manuscript has not been published previously (partly or in full), except in an abstract form, (3) a single study is not split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time, (4) no data have been fabricated or manipulated (including images) to support your conclusions, (5) no data, text, or theories by others are presented as if they were the author{\textquoteright}s own (“plagiarism”), and (6) proper acknowledgements to other works have been given. The authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results. Upon request, the authors are prepared to send relevant documentation or data in order to verify the validity of the results. This could be in the form of raw data, samples, records, etc.To ensure objectivity and transparency in research and to ensure that accepted principles of ethical and professional conduct have been followed, the authors have included information regarding sources of funding and potential conflicts of interest (financial or non-financial). This work was supported by USF OR&I HSC-18330 & COM HSC-18300 (YK), NIH NINDS RO1 1R01NS071956-01 (CVB), James and Esther King Biomedical Research Program 09 KB-01-23123 (CVB) and 1KG01-33966 (CVB), and USF Department of Neurosurgery and Brain Repair Funds (CVB). Funding Information: This work was supported by USF OR&I HSC-18330 & COM HSC-18300 (YK), NIH NINDS RO1 1R01NS071956-01 (CVB), James and Esther King Biomedical Research Program 09 KB-01-23123 (CVB) and 1KG01-33966 (CVB), and USF Department of Neurosurgery and Brain Repair Funds (CVB). Part of this manuscript was presented as an abstract, “Golgi complex fragmentation/dispersal initiates neuronal aggravation in epilepsy: Reelin poses as a potential therapeutic target” at the American Society for Neural Therapy and Repair 21st Annual Conference, April 24–26, 2014, Clearwater, Florida. Publisher Copyright: {\textcopyright} 2015, The Author(s).",
year = "2016",
month = apr,
day = "1",
doi = "10.1007/s12035-015-9126-1",
language = "English (US)",
volume = "53",
pages = "1874--1883",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "3",
}