The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS
The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS
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DOI：
10.1046/j.1471-4159.1999.720879.x
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发表时间：
1999-02-01
影响因子：
4.7
通讯作者：
Manji, HK
中科院分区：
文献类型：
--
作者：
Chen, G;Zeng, WZ;Manji, HK
mRNA的差异显示被用来确定由两种情绪稳定剂，锂和丙戊酸盐（VPA）诱导的基因表达的一致性变化。两种治疗，在慢性给药，增加转录因子多瘤病毒增强子结合蛋白（PEBP）2 β在额叶皮层（FCx）的mRNA水平。两种处理还增加了PEBP 2 α β的DNA结合活性，并显著增加了FCx中bcl-2（已知由PEBP 2转录调节）的水平。免疫组织化学研究显示，在FCx的第2层和第3层的bcl-2免疫反应细胞的数量显着增加。这些新的发现代表了药物诱导的CNS bcl-2水平增加的首次报道，不仅可能对情绪障碍有影响，而且可能对各种神经退行性疾病的长期治疗有影响。
Differential display of mRNA was used to identify concordant changes in gene expression induced by two mood-stabilizing agents, lithium and valproate (VPA). Both treatments, on chronic administration, increased mRNA levers of the transcription factor polyomavirus enhancer-binding protein (PEBP) 2 beta in frontal cortex (FCx). Both treatments also increased the DNA binding activity of PEBP2 alpha beta and robustly increased the levels of bcl-2 (known to be transcriptionally regulated by PEBP2) in FCx. Immunohistochemical studies revealed a marked increase in the number of bcl-2-immunoreactive cells in layers 2 and 3 of FCx. These novel findings represent the first report of medication-induced increases in CNS bcl-2 levels and may have implications not only for mood disorders, but also for long-term treatment of various neurodegenerative disorders.