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Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment.Methods We used quantitative RT-PCR apoptosis-focused gene arrays(96-well,84 apoptosis related genes)to assess changes of gene expression in the cochlear basilar membrane(hair cells-supporting cells)and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 μM mefloquine for 3 h.Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane,and in 32 genes in the spiral ganglion neurons compared with time-matched controls.The responding genes could be classified as pro-or anti-apoptotic,and were mainly implicated in the Bcl-2,Caspase,Card,IAP,TNF ligand / TNF receptor,Death domain / Death effector domain,DNA damage / p53,and NF-kappa B families.Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in the death receptor-mediated signaling pathway and apoptotic mitochondrial pathway.In addition,it was found that numerous anti-apoptotic genes such as Bcl2a1,Birc1b,Birc3,Birc4,Bnip1,Cflar,Il10,Lhx4,Mcl1,Nfkb1,Prlr,Prok2,and TNF were greatly up-regulated in the cochlear tissue,which might imply the co-existence of protective response in the cells at the early stage of mefloquine-induced damage.