[Okadaic acid induces the expression of glutamate transporter EAAT1 in the neurons of rat brain].
To study the relationship between tau hyperphosphorylation and the function of glutamate transporter okadaic acid (OA), a protein phosphatase inhibitor, 20 ng in a 0.5 microl 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 3 d after the injection. However, most neurons in the peri-injected areas showed normal morphological characters with immuno positive reaction for AT8, a tau phosphorylated marker; (2) morphological analysis showed that tau hyperphosphorylation caused by OA treatment was mainly observed in the axons and dendrites of neuronal cells at 6 h in the cell body at 1 d, which brought about dystrophic 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 12 h (P<0.01), peaked at 1 d (P<0.001), then decreased at 3 d 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.
State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032.
Jian-She
JS
Wei
Ling-Mei
LM
Zhang
Ya-Lin
YL
Huang
Cui-Qing
CQ
Zhu
Feng-Yan
FY
Sun
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D016875:tau Proteins / Q000378:metabolism
D027341:Excitatory Amino Acid Transporter 1; C493392:Slc1a3 protein, rat; D016875:tau Proteins; D019319:Okadaic Acid