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Possible Involvement of Astrocytes in Neuroprotection by the Cognitive Enhancer T-588

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Abstract

We have previously shown that the cognition enhancer (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588) protects astrocytes against hydrogen peroxide (H2O2) injury via activation of extracellular signal-regulated kinase (ERK) pathway. The present study examines whether the effect of T-588 on astrocytes contributes to neuroprotection in neuronal injury models. Astrocyte-conditioned medium (ACM) protected against neuronal injury induced by amyloid-β protein (Aβ) in cultured cortical neurons. The effect of ACM on Aβ-induced injury was blocked by the ERK kinase inhibitor 2′-amino-3′-methoxyflavone. ACM stimulated ERK phosphorylation in cultured neurons. ACM derived from astrocytes exposed to H2O2 lost the activities to stimulate ERK phosphorylation and protect against neuronal injury. T-588 blocked the H2O2-induced loss of the activities of ACM. These results suggest that ACM protects against neuronal injury by an ERK-dependent mechanism, and the effect of T-588 on astrocytic injury results in neuroprotection.

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Authors and Affiliations

  1. Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

    Akiko Yamamuro & Yukio Ago

  2. Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan

    Akiko Yamamuro & Sadaaki Maeda

  3. Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Kobe, Japan

    Kazuhiro Takuma

  4. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

    Yoshiyuki Sakai & Akemichi Baba

  5. Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

    Toshio Matsuda

Authors
  1. Akiko Yamamuro
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  2. Yukio Ago
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  3. Kazuhiro Takuma
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  4. Sadaaki Maeda
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  5. Yoshiyuki Sakai
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  6. Akemichi Baba
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  7. Toshio Matsuda
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Correspondence to Toshio Matsuda.

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Yamamuro, A., Ago, Y., Takuma, K. et al. Possible Involvement of Astrocytes in Neuroprotection by the Cognitive Enhancer T-588. Neurochem Res 28, 1779–1783 (2003). https://doi.org/10.1023/A:1026103304490

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  • DOI: https://doi.org/10.1023/A:1026103304490

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