BDNF-DT和BDNF-AS-DT:在BDNF位点中的新基因
Svitlana V Bach1, Giovanna Punzi1,2, Nuri E Smith1
1Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore (MD), USA.
medRxiv : the preprint server for health sciences
|August 12, 2025
概括
研究人员发现了新的分离转录 (DT),BDNF-DT和BDNF-AS-DT,与BDNF基因调节有关. 这些转录显示了精神分裂症的改变表达,这表明它在疾病和神经元发育中的作用.
科学领域:
- 基因组学和神经生物学
- 基因调控和基因表达的调节和表达
背景情况:
- 从双向促进体的分离转录在真核生物中很常见,但分离转录 (DT) 的功能仍然不清楚.
- BDNF基因对神经元发育,分化和突触可塑性至关重要.
研究的目的:
- 识别和描述BDNF位点中的新型分离转录.
- 研究这些转录在神经元功能和疾病中的生物相关性和调控作用.
主要方法:
- 使用基因组和转录组分析识别和描述BDNF-DT和BDNF-AS-DT.
- 对人类死后脑组织 (DLPFC) 和神经前代细胞中的基因表达的分析.
- 以CRISPR为媒介的基因编辑来评估监管效应.
- 与精神分裂症患者的临床数据的相关性分析.
主要成果:
- 独立于BDNF-AS的BDNF-DT显示出发育调节和与人类DLPFC中BDNF表达的正相关性.
- 在神经元脱极化后,BDNF-DT和BDNF-AS-DT的表达增加,遵循BDNF表达动态.
- 由CRISPR诱导的BDNF上调调节驱动BDNF-DT的表达.
- 在精神分裂症患者的DLPFC中,BDNF-DT的调高;较低的BDNF-AS-DT表达与精神分裂症和特定的SNP (rs6265) 有关.
结论:
- BDNF-DT和BDNF-AS-DT是BDNF位点内的新型调节元素.
- 这些转录在BDNF调节中发挥作用,并与精神分裂症风险有关.
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