线性与宏循环GBCA对小鼠中枢神经系统基因表达的长期影响
Chuanbing Wang1, Yuxia Tang1, Jiajia Tang1
1Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
European radiology experimental
|January 10, 2025
概括
线性剂的慢性加多保留会改变小鼠大脑的基因表达,影响神经炎症路径. 宏循环药物没有显示这些长期影响,这表明不同的安全性.
科学领域:
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
- 医疗成像医学成像
背景情况:
- 基于加多的对比剂 (GBCA) 在MRI中被广泛使用.
- 人们对中枢神经系统 (CNS) 中长期保留加多存在担忧.
- 不同GBCA类型 (线性与宏循环) 对基因表达的影响尚未完全理解.
研究的目的:
- 调查慢性加多保留对小鼠中枢神经系统基因表达的长期影响.
- 为了比较线性 (gadodiamide) 与宏环 (gadobutrol) GBCAs的影响.
- 为了确定受加多沉积影响的特定分子通路.
主要方法:
- 小鼠每周注射线性 (加多胺) 或宏环 (加多布托罗尔) GBCA,或盐水,在一定的时间内.
- 大脑和脊髓中的加多水平使用ICP-MS在一年的洗后进行测量.
- RNA测序和生物信息分析确定了差异表达基因 (DEG) 和丰富的通路.
- 基因表达的变化被验证使用qRT-PCR和Western blot.
主要成果:
- 在线性GBCA重复服用后,在大脑和脊髓中观察到加多的保留.
- RNA测序显示,在1年后,加多胺组的大脑和脊髓中有17个共享的DEG.
- 证实了Hmgb2和Sgk1的改变表达,与神经炎症通路的丰富.
- 在宏环GBCA或早期时间点组中没有检测到显著的基因表达变化.
结论:
- 从线性GBCA中慢性加多沉积显著改变了小鼠中枢神经系统中的基因表达.
- 神经炎症通路受到线性药物长期保留加多的显著影响.
- 这些发现强调了评估不同类型GBCA的长期安全的重要性.
相关概念视频
GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...


