Possible involvement of astrocytes in neuroprotection by the cognitive enhancer T-588.
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-beta protein (A beta) in cultured cortical neurons. The effect of ACM on A beta-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.
Yamamuro
Akiko
A
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Ago
Yukio
Y
Takuma
Kazuhiro
K
Maeda
Sadaaki
S
Sakai
Yoshiyuki
Y
Baba
Akemichi
A
Matsuda
Toshio
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004048:Diethylamines / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D004048:Diethylamines; D013876:Thiophenes; C082372:T 588