Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2009 -2011
Author : TANIMUKAI Hitoshi; KUDO Takashi; MORIHARA Takashi; OKAMOTO Yoshiaki; TSUGANE Mamiko
To investigate the molecular mechanisms of chemotherapy induced cognitive impairment, we studied the neuronal toxicity(NT) of paclitaxel(Px), fluorouracil(5-FU), and cyclophosphamide(CPA) on neuronal culture cells(SY5Y and SK-N-SH) and further investigated its relationship to endoplasmic reticulum stress(ER stress). Significant NT was observed in cells treated with Px and 5-FU in dose dependent manner, but not with CPA. In addition, the induction of both p-eIF2αand GRP78/ 94 were observed in cells by Px or 5-FU treatment. Pre-treatment of cells with Bip inducer X(BIX) reduced Px-induced NT but not 5-FU induced NT. These data suggest that Px induced NT probably relates to ER stress and BIX could prevent the Px induced NT as including chemobrain.