Translocation of glutamate transporter subtype excitatory amino acid carrier 1 protein in kainic acid-induced rat epilepsy

Akiko Furuta, Mami Noda, Satoshi Suzuki, Yoshinobu Goto, Yoshiko Kanahori, Jeffrey D. Rothstein, Toru Iwaki

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Abstract

Glutamate excitotoxicity has been implicated in the pathophysiology of epilepsy. Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. We examined the temporal expression of the sodium-dependent neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), in KA-induced rat epilepsy. As an early alteration, perinuclear deposits of EAAC1 protein were found mainly in the large pyramidal neurons at the hippocampus, neocortex, piriform cortex, and amygdala with the reduction of neuropil staining 6 hours after KA injection. Immunoelectron microscopic study revealed that the perinuclear EAAC1 immunoreactivity corresponded to the translocation to the Golgi complex. At this time point, EAAC1 mRNA was down-regulated. The intracellular aggregation of EAAC1 primarily disappeared by 24 hours. In vitro studies indicated that internalization of EAAC1 from the plasma membrane to the intracellular compartment by KA treatment was associated with the reduction of electrogenic transporter currents. Our results suggest that the transient EAAC1 internalization participates in the modulation of the transporter function preventing excessive glutamate uptake to pyramidal neurons during the early stage of epilepsy.

Original languageEnglish
Pages (from-to)779-787
Number of pages9
JournalAmerican Journal of Pathology
Volume163
Issue number2
DOIs
Publication statusPublished - Aug 1 2003

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Amino Acid Transport System X-AG
Excitatory Amino Acids
Kainic Acid
Epilepsy
Carrier Proteins
Pyramidal Cells
Glutamic Acid
Injections
Neuropil
Temporal Lobe Epilepsy
Neocortex
Golgi Apparatus
Amygdala
Hippocampus
Animal Models
Sodium
Cell Membrane
Staining and Labeling
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Translocation of glutamate transporter subtype excitatory amino acid carrier 1 protein in kainic acid-induced rat epilepsy. / Furuta, Akiko; Noda, Mami; Suzuki, Satoshi; Goto, Yoshinobu; Kanahori, Yoshiko; Rothstein, Jeffrey D.; Iwaki, Toru.

In: American Journal of Pathology, Vol. 163, No. 2, 01.08.2003, p. 779-787.

Research output: Contribution to journalArticle

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