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  • Title: Astrocytic glutamate transporter-dependent neuroprotection against glutamate toxicity: an in vitro study of maslinic acid.
    Author: Qian Y, Guan T, Tang X, Huang L, Huang M, Li Y, Sun H, Yu R, Zhang F.
    Journal: Eur J Pharmacol; 2011 Jan 25; 651(1-3):59-65. PubMed ID: 21118675.
    Abstract:
    The astrocytic glutamate transporters GLAST/EAAT1 and GLT-1/EAAT2 are crucial for the removal of glutamate from the synaptic cleft and are essential for maintaining a low concentration of extracellular glutamate in the brain. Enhanced transporter expression is neuroprotective. In the present study, we tested the neuropotective effects of maslinic acid, a natural product from the Olea europaea plant, on cultures of primary neurons from the cerebral cortex. Studies showed that astrocyte-conditioned medium from maslinic acid-treated astrocytes dose-dependently promoted neuron survival during glutamate toxicity by enhancing extracellular glutamate clearance. Real-time PCR and western blot analysis revealed that maslinic acid pre-treatment significantly increased the expression of GLAST and GLT-1 at the protein and mRNA levels. In addition, this neuroprotection was abolished by the glutamate transporter inhibitor, L-Threohydroxy aspartate (THA), in a co-culture of astrocytes and neurons. These findings suggest that maslinic acid regulates the extracellular glutamate concentration by increasing the expression of astrocytic glutamate transporters, which may, in turn, provide neuroprotection.
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