Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Neurobiol Dis. 2010 Mar;37(3):596-603. doi: 10.1016/j.nbd.2009.11.010. Epub 2009 Nov 26.
Bipolar disorder (BD) is a progressive psychiatric disorder characterized by recurrent changes of mood and is associated with cognitive decline. There is evidence of excitotoxicity, neuroinflammation, upregulated arachidonic acid (AA) cascade signaling and brain atrophy in BD patients. These observations suggest that BD pathology may be associated with apoptosis as well as with disturbed synaptic function. To test this hypothesis, we measured mRNA and protein levels of the pro-apoptotic (Bax, BAD, caspase-9 and caspase-3) and anti-apoptotic factors (BDNF and Bcl-2) and of pre- and post-synaptic markers (synaptophysin and drebrin), in postmortem prefrontal cortex (Brodmann area 9) from 10 BD patients and 10 age-matched controls. Consistent with the hypothesis, BD brains showed significant increases in protein and mRNA levels of the pro-apoptotic factors and significant decreases of levels of the anti-apoptotic factors and the synaptic markers, synaptophysin and drebrin. These differences may contribute to brain atrophy and progressive cognitive changes in BD.
双相情感障碍（BD）是一种以情绪反复变化为特征的进行性精神障碍，与认知能力下降有关。BD 患者存在兴奋性毒性、神经炎症、花生四烯酸（AA）级联信号上调和脑萎缩的证据。这些观察结果表明，BD 病理学可能与细胞凋亡以及突触功能紊乱有关。为了验证这一假设，我们测量了 10 名 BD 患者和 10 名年龄匹配的对照者死后前额叶皮质（布罗德曼 9 区）中促凋亡（Bax、BAD、caspase-9 和 caspase-3）和抗凋亡因子（BDNF 和 Bcl-2）以及突触前和突触后标志物（突触素和 drebrin）的 mRNA 和蛋白水平。与假设一致，BD 大脑中促凋亡因子的蛋白和 mRNA 水平显著增加，而抗凋亡因子和突触标志物突触素和 drebrin 的水平显著降低。这些差异可能导致 BD 中的脑萎缩和进行性认知变化。
