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Okadaic acid induces the expression of glutamate transporter EAAT1 in the neurons of rat brain

Wei Jianshe, Zhang Lingmei, Huang Yalin, Zhu Cuiqing, Sun Fengyan

State Key Laboratory of Medical neurobiology, Shanghai Medical College, Fudan University.Shanghai(200032)

Abstract

To study the relationship between tau hyperphosphorylation and the function of glutamate transporter okadaic acid (OA), a protein phosphatase inhibitor, 20 ng in a 0.5μl volume, was injected into the frontal cortex of rat brain and immunostaining was used to observe the phosphorylation of tau protein and the expression of excitatory amino acid transporter 1 (EAAT1) in the brain following the injection. The results showed that (1) the neurons in the center of the injection region displayed cytoplasmic shrinkage, swelling, nuclear pyknosis, and dislocation at the early stage, and necrosis appeared 3d after the injection. However, most neurons in the peri-injected areas showed normal morphological characters with immuno-positive reation for AT8, a tau phosphorylated marker; (2) morphological analysis showed that tau hyperphosphorlation caused by OA treatment was mainly observed in the axons and dendrites of neuronal cells at 6h in the cell body at 2d, which brought about dystropjic neurites and neurofibrillary tangle (NFT)-like pathological changes; (3) the induction of glutamate transporter EAAT1 was observed in the involved areas corresponding to that with AT8 immunopositive staining, and the number of EAAT1-positive staining cells markedly increased at 12h (P<0.01), peaked at 1d (P<0.001), then decreased at 3d following the injection. Combined with a confocal laser scanning microscopic analysis, double fluorescent immunostaining showed that EAAT1 positive staining appeared in neurons as well as astrocytes in the peri-injected areas of the frontal cortex. These results demonstrate that OA increases glutamate transporter EAAT1 expression in neurons while it induces tau hyperphosphorylation. However, the mechanism and significance of the induction of glutamate transporter EAAT1 expression remain to be further elucidated.

Key words: Okadaic acid;Tau protein;Phosphorylation;Neurofibrillary tangle(NFT);Excitatory amino acid transporter 1(EAATl)

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Citing This Article：

Wei Jianshe, Zhang Lingmei, Huang Yalin, Zhu Cuiqing, Sun Fengyan. Okadaic acid induces the expression of glutamate transporter EAAT1 in the neurons of rat brain. Acta Physiol Sin 2002; 54 (4): (in Chinese with English abstract).