Morita Kyoji, Arimochi Hideki, Her Song
Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Brain Res Mol Brain Res. 2005 Oct 3;139(2):193-200. doi: 10.1016/j.molbrainres.2005.05.013.
Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain.
选择性5-羟色胺再摄取抑制剂（SSRIs）被广泛用于治疗抑郁情绪障碍，并且众所周知其可抑制神经递质5-羟色胺再摄取进入神经末梢。因此，似乎可以想象这些药物可能由于抑制再摄取而导致5-羟色胺从突触流出，从而刺激神经末梢周围的神经胶质细胞。基于这一假设，作为研究SSRIs对神经胶质细胞间接影响的体外模型实验之一，检测了5-羟色胺对大鼠C6胶质瘤细胞中甾体5α-还原酶1型（5α-R）基因表达的影响。5-羟色胺通过刺激5-羟色胺5-HT2A受体提高了5α-R mRNA和蛋白质水平，并且在胶质瘤细胞中5α-R基因表达之前也提高了Egr-1 mRNA和蛋白质水平。此外，在预先加载了针对Egr-1基因的反义寡脱氧核苷酸的细胞中，5-羟色胺未能显著增加5α-R mRNA水平。这些结果表明，5-羟色胺可能通过转录因子Egr-1刺激神经胶质细胞中的5α-R基因表达，从而提示从5-羟色胺能突触流出的5-羟色胺可能与SSRIs诱导的脑内神经甾体代谢变化有关。
