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

Yuji Kaneko, Robert Sullivan, Travis Dailey, Fernando Vale Diaz, Naoki Tajiri, Cesar V. Borlongan

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1874-1883
Number of pages10
JournalMolecular Neurobiology
Volume53
Issue number3
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Fingerprint

Kainic Acid
Golgi Apparatus
Proteolysis
Epilepsy
Glycosylation
Lysosomes
Endoplasmic Reticulum
Inhibitory Concentration 50
Half-Life
Rodentia
Cell Death
Biomarkers
In Vitro Techniques
Neurons

Keywords

  • Glycosylation
  • Golgi protein
  • Initiating epilepsy
  • Kainic acid
  • Primary rat neuronal cell

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

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. / Kaneko, Yuji; Sullivan, Robert; Dailey, Travis; Vale Diaz, Fernando; Tajiri, Naoki; Borlongan, Cesar V.

In: Molecular Neurobiology, Vol. 53, No. 3, 01.04.2016, p. 1874-1883.

Research output: Contribution to journalArticle

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