双相障碍患者诱导多能干细胞、神经干细胞和尸检脑组织中 BDNF 而非 BDNF-AS 的异常基因表达。
Abnormal gene expression of BDNF, but not BDNF-AS, in iPSC, neural stem cells and postmortem brain samples from bipolar disorder.
机构信息
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
出版信息
J Affect Disord. 2021 Jul 1;290:61-64. doi: 10.1016/j.jad.2021.04.042. Epub 2021 May 3.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) antisense RNA (BDNF-AS) was identified as naturally conserved non-coding antisense RNA that suppresses the transcription of BDNF.
METHODS
We measured the expression of BDNF mRNA and BDNF-AS mRNA in iPSC and NSC from bipolar disorder (BD) patients and healthy control subjects, and postmortem brain samples such as the corpus callosum, the Brodmann area (BA8), and BA46 from BD patients and age- and sex-matched controls.
RESULTS
The expression of BDNF mRNA in iPSC from BD patients (n = 6) was significantly lower than that of control subjects (n = 4) although the expression of BDNF mRNA in NSC from BD patients was significantly higher than that of control subjects. In contrast, there were no changes in the expression of BDNF-AS mRNA in both iPSC and NSC between two groups. The expression of BDNF mRNA in the BA46 from BD patients (n = 35) was significantly lower than that of controls (n = 34) although the expression of BDNF mRNA in the corpus callosum and BA8 was not different between two groups (n = 15). In contrast, there were no changes in expression of BDNF-AS mRNA in the three brain regions between two groups. Interestingly, there were significant positive correlations between BDNF mRNA expression and BDNF-AS mRNA expression in the postmortem brain samples.
LIMITATIONS
Sample sizes are relatively low.
CONCLUSIONS
Our data suggest that abnormalities in the expression of BDNF, but not BDNF-AS, play a role in the pathogenesis of BD.
背景
脑源性神经营养因子（BDNF）反义 RNA（BDNF-AS）被鉴定为天然保守的非编码反义 RNA，可抑制 BDNF 的转录。
方法
我们测量了双相障碍（BD）患者和健康对照者的 iPSC 和 NSC 中 BDNF mRNA 和 BDNF-AS mRNA 的表达，以及来自 BD 患者和年龄、性别匹配对照者的胼胝体、布罗德曼区（BA8）和 BA46 等死后脑组织样本中的表达。
结果
BD 患者 iPSC 中的 BDNF mRNA 表达（n=6）明显低于对照组（n=4），尽管 BDNF 患者 NSC 中的 BDNF mRNA 表达明显高于对照组。相比之下，两组间 iPSC 和 NSC 中 BDNF-AS mRNA 的表达均无变化。BD 患者 BA46 中的 BDNF mRNA 表达（n=35）明显低于对照组（n=34），而胼胝体和 BA8 中 BDNF mRNA 的表达在两组间无差异（n=15）。相比之下，两组间三个脑区的 BDNF-AS mRNA 表达均无变化。有趣的是，死后脑组织样本中 BDNF mRNA 表达与 BDNF-AS mRNA 表达之间存在显著的正相关。
局限性
样本量相对较低。
结论
我们的数据表明，BDNF 表达异常，而不是 BDNF-AS，在 BD 的发病机制中起作用。
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