6月龄野生型和APP/PS1转基因小鼠海马和皮层神经递质代谢组学研究
作者:
作者单位:

作者简介:

通讯作者:

基金项目:

国家重点研发计划(2018YFA0108503);首都卫生发展科研专项(首发 2020-2Z-1034)


Neurotransmitter metabolomics research on the hippocampus and cortex of six-month-old wild-type and APP/PS1 transgenic mice
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的 探讨 6 月龄 APP/PS1 转基因小鼠相较于同月龄野生型小鼠海马和皮层组织神经递 质代谢物的变化。方法 选取健康雌性 6 月龄野生型和 APP/PS1 转基因小鼠各 8 只,3 只进行刚果红实 验,5 只利用超高效液相色谱串联质谱方法分析海马和皮层组织中神经递质代谢物的含量。在正交偏 最小二乘判别分析(OPLS-DA)模型主成分的差异权重贡献值(VIP)≥1的基础上,以独立样本t检验P<0.05 或差异倍数(FC)值≥ 1.2 或 FC 值≤ 0.8,筛选组间差异代谢物。结果 6 月龄 APP/PS1 转基因小鼠海马 和皮层组织中出现 β 淀粉样蛋白沉积;两组小鼠的海马和皮层代谢轮廓呈现分离趋势。在小鼠海马 中鉴定出 17 种差异代谢物,分别为肾上腺素、去甲肾上腺素、左旋多巴、多巴胺、3,4- 二羟基苯乙酸酯 (DOPAC)、3,4- 二羟苯基二醇、3,4- 二羟基扁桃酸、甲氧基去甲肾上腺素(NMN)、4- 羟基 -3- 甲氧基苯 乙二醇(MHPG)、4- 羟基 -3- 甲氧基 - 扁桃酸 / 高香草酸(HVA)、谷氨酰胺、谷氨酸、γ- 氨基丁酸、5- 羟 色胺(5-HT)、羟基吲哚乙酸(5-HIAA)、鸟氨酸、酪胺;在小鼠皮层中鉴定出 12 种差异代谢物,分别为多巴 胺、DOPAC、NMN、3- 甲氧酪胺、MHPG、HVA、5-HT、5-HIAA、乙醇胺、L- 酪氨酸、L- 苯丙氨酸、苏氨酸。 结论 APP/PS1 转基因小鼠海马和皮层神经递质代谢种类趋势变化不同,可能作为 APP/PS1 转基因小 鼠认知功能障碍早期病理改变的靶点。

    Abstract:

    Objective To analyze the changes of neurotransmitter metabolites in the hippocampus and cortex of six-month-old APP/PS1 transgenic mice and wild-type mice of the same age. Methods A total of 8 healthy female 6-month-old wild-type mice and 8 APP/PS1 transgenic mice were selected. Congo red test was conducted in 3 mice, and ultrahigh performance liquid chromatography tandem mass spectrometry was used to analyze the content of neurotransmitter metabolites in hippocampus and cortex in 5 mice. The difference metabolites between groups were screened by independent sample t test P< 0.05 or the fold change (FC) ≥ 1.2 or FC ≤ 0.8, on the basis of variable influence on projection (VIP) ≥ 1 of the principal component of orthogonal partial least squares discriminant analysis (OPLS-DA) model. Results Amyloid-β protein deposition appears in hippocampus and cortex of 6-month-old APP/PS1 transgenic mice. The metabolic profiles of hippocampus and cortex of the two groups of mice showed a trend of separation. A total of 17 different metabolites were identified in the hippocampus of mice, including epinephrine, norepinephrine, levodopa, dopamine, 3, 4-dihydroxyphenylacetate (DOPAC), 3,4-dihydroxyphenyldiol, 3,4-dihydroxymandelic acid, methoxy norepinephrine (NMN), 4-hydroxy-3-methoxyphenylene glycol (MHPG), 4-hydroxy-3-methoxy-mandelic acid/homovanillic acid (HVA), glutamine, glutamate γ-aminobutyric acid, 5-hydroxytryptamine (5-HT), hydroxyindoleacetic acid (5-HIAA), ornithine and tyramine. A total of 12 different metabolites were identified in the cortex of mice, including dopamine, DOPAC, NMN, 3-methoxy tyramine, MHPG, HVA, 5-HT, 5-HIAA, ethanolamine, L-tyrosine, L-phenylalanine and threonine. Conclusions The trend of neurotransmitter metabolism in hippocampus and cortex of APP/PS1 transgenic mice is different, which can be used as the target of early pathological changes in cognitive dysfunction of APP/PS1 transgenic mice.

    参考文献
    相似文献
    引证文献
引用本文

康美美,吕彩珍,王蓉.6月龄野生型和APP/PS1转基因小鼠海马和皮层神经递质代谢组学研究[J].神经疾病与精神卫生,2022,22(11):
DOI :10.3969/j. issn.1009-6574.2022.11.004.

复制
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2022-12-22