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

Molecular Neurobiology
Yuji KanekoCesar V Borlongan

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 (IC 50) 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 represe...Continue Reading

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Citations

Feb 5, 2016·CNS Neuroscience & Therapeutics·Naoki TajiriCesar V Borlongan
Apr 12, 2016·Frontiers in Cellular Neuroscience·April L LussierG William Rebeck
Feb 22, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Yuji KanekoCesar V Borlongan
Oct 22, 2016·Scientific Reports·Yuji KanekoCesar V Borlongan
Apr 1, 2016·Journal of Alzheimer's Disease : JAD·Inmaculada Cuchillo-IbañezJavier Sáez-Valero
May 28, 2019·Frontiers in Cell and Developmental Biology·Mario O CaracciMaría-Paz Marzolo

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Datasets Mentioned

BETA
GM130
GM
130

Methods Mentioned

BETA
protein folding
glycosylation

Software Mentioned

GraphPad Prism

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