Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide

M. Noda, H. Nakanishi, N. Akaike

研究成果: ジャーナルへの寄稿記事

125 引用 (Scopus)

抄録

In the present study, we found that amyloid-β peptide enhanced glutamate release from primary cultured rat microglia via the Na+-dependent glutamate transporter, which was activated by extracellular K+. Glutamate transport current was measured by a conventional whole-cell patch recording mode under voltage-clamp conditions. With the pipette solution containing 10 mM glutamate and 100 mM Na+, an increase of the external K+ concentration from 0 to 10 mM evoked an outward current, resulting from co-extrusion of glutamate and Na+. The inward current, reflecting forward glutamate transport, was also activated by external glutamate. Both these reverse and forward glutamate transport currents were three-fold greater in microglia incubated with a relatively low concentration of amyloid-β peptide (25-35) (5 μM) for four days. The glutamate-activated inward current was blocked by D,L-threo-β-hydroxyaspartate in a dose-dependent manner (ranging from 0.001 to 1 mM), but not by a high concentration of kainate (1 mM). The glutamate concentration released from microglia upon high-K+ stimulation was also significantly increased (up to 170 μM) after treatment with amyloid-β peptide (25-35). These results suggest that, at the pathological sites where extracellular K+ concentration may increase, the activation of microglia by amyloid-β peptide causes an increase in extracellular glutamate concentration via reverse glutamate transporter, and therefore this mechanism may contribute to the pathogenesis of neuronal dysfunction and death in Alzheimer's disease.

元の言語英語
ページ(範囲)1465-1474
ページ数10
ジャーナルNeuroscience
92
発行部数4
DOI
出版物ステータス出版済み - 6 1 1999

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Amino Acid Transport System X-AG
Amyloid beta-Peptides
Microglia
Glutamic Acid
Amyloid
Peptides
Kainic Acid
Patch-Clamp Techniques
Alzheimer Disease

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. / Noda, M.; Nakanishi, H.; Akaike, N.

:: Neuroscience, 巻 92, 番号 4, 01.06.1999, p. 1465-1474.

研究成果: ジャーナルへの寄稿記事

Noda, M. ; Nakanishi, H. ; Akaike, N. / Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. :: Neuroscience. 1999 ; 巻 92, 番号 4. pp. 1465-1474.
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